In its flaccid state, the penis acts as a tube through which urine is passed directly from the bladder via the urethra. The urethra is also a conduit for the ejaculate, which can be expelled by the penis in both its flaccid and erect state. The penile urethra is encased by a sleeve of erectile tissue called the corpus spongiosum, which expands at the tip of the penis forming the glans and at the base forming the bulb. The function of the spongiosum is to maintain the patency of the urethra during sexual activity so that the ejaculate is not prevented from being expelled by a collapsed structure. The main erectile components of the penis are the left and right corpora cavernosa that communicate via perforations to affect a single erectile chamber. These two connecting bodies attach to the rami of the pelvis after turning through a surprisingly sharp angle to become the deep erectile crura.

Through the core of both cavernosa run the cavernosal arteries, which are branches of the internal pudendal artery, itself a branch of the internal iliac artery. The cavernosal arteries give rise to numerous helicine (spiral) artery branches. These channel blood into the trabeculae of smooth muscle that makes up the walls of the tiny sinusoids of the cavernosa. The walls of the artery and the sinusoids are lined by nitric oxide (NO) producing endothelial cells. The sinusoids drain into subtunical veins that lie on the inside of the tunica albuginea, which forms a tough, noncompliant layer around each of the erectile bodies. Blood escapes this boundary by passing through emissary veins that pierce it. Blood continues its journey through circumflex veins that surround the outside of the tunica albuginea and are sandwiched between it and the "Buck’s fascia." They then drain into the deep dorsal vein on the upper surface of the penis. The other major arteries, veins, and nerves of the penis lie dorsally. The complexities of the penile machinery are encased in the thin superficial "Colles’ facia," which in turn is surrounded by the subcutaneous cellular tissue and skin.

The nervous system of the penis is in three parts. The parasympathetic nerves are branches of spinal nerves S2–S4, which give rise to the so-called pelvic splanchnic nerves that pass around the posterior aspect of the prostate gland, forming the prostatic plexus. Passing forward, they form the cavernous nerves, which branch into the body of the penis. It is this parasympathetic system that is able to elicit an erection. The sympathetic nerves are branches of the sympathetic chain at levels T11–L2. These pass through the inferior mesenteric plexus, the superior hypogastric plexus, and the pelvic plexus and branch off to the organs involved in ejaculation. Overactivity of the sympathetic system (e.g., in the stressed individual) maintains a persistent state of detumescence, although not all sympathetic activity is inhibitory. The sensory nerves of the penis and scrotum are all branches of the pudendal nerve, which can be traced back to branches of S2–S4. With these systems in mind, it can be seen that an erection can be initiated by two independent mechanisms. The first requires tactile stimulation of the penis. The nerve impulses synapse in the spinal cord and form a reflex arc with nerves of the parasympathetic system responsible for the erectile response. The other mechanism involves the higher centers of the brain that interpret sensory and fantasy stimuli triggering an erotic response resulting in an erection. The erection starts with the stimulation of one or both of these systems in a neuronally modulated hemodynamic response.

The exact mechanism of neurotransmission in the erectile response is not yet fully understood. It appears, however, that a few neurotransmitters are of key importance. Nerve endings of the parasympathetic system release acetylcholine (ACh), which appears to have a modulatory effect but no direct action; vasoactive intestinal peptide (VIP) is also released, causing tumescence but not erection; release of NO does cause erection. These neurotransmitters have all been isolated in penile erectile tissue, and the NO system is the one exploited by some of the current erectogenic oral preparations. NO is a potent smooth muscle relaxant and vasodilator produced by neurons and endothelial cells that contain the enzyme nitric oxide synthase (NOS). The effect of NO is to increase the amount of cyclic guanosine monophosphate (cGMP) available in the smooth muscle. cGMP is a second messenger that is utilized in a cascade system in which the intracellular concentration of calcium ions is diminished so that the calcium dependent muscle relaxes. It has previously been noted that the erectile response can be very rapid and synchronized, and it has been found that individual smooth muscle cells are able to communicate directly with each other via gap junctions.

There is another similar second messenger system that utilizes cyclic adenosine monophosphate (cAMP). In cavernosal tissue, the controlling factors for levels of cAMP are prostaglandins. PGE1 activates prostanoid receptors, which stimulate adenylate cyclase to produce cAMP. Here again, the effect is to reduce the levels of intracellular calcium and produce smooth muscle relaxation. There are other pharmacological agents that employ this alternative mechanism to elicit an erection.

In order for a sustained erection to occur, there must be: dilatation of the arteries to allow more blood to enter the penis; engorgement of the sinusoids to establish rigidity; narrowing of the venous system to prevent blood leaking back out. The simple relaxation of smooth muscle is able to achieve this. The smooth muscle in the artery wall relaxes and the artery vasodilates. At the same time, the trabecular smooth muscle relaxes and blood is allowed to fill the enlarged sinusoids. As the pressure rises, the penis becomes more tumescent and the subtunical venules become compressed between the collagenated smooth muscle and the tunica albuginea, so that outflow is diminished. Hydraulic pressure within the cavernosa increases to about 100 mmHg so that the penis hardens and becomes fully erect. Further reflex contraction of the ischiocavernous muscles during sexual intercourse or masturbation produces a rigid erection with internal pressures of several hundred millimeters of mercury. The activation of the sympathetic nervous system, which occurs at ejaculation, releases the neurotransmitters norepinephrine, endothelin, and neuropeptide Y. These have an opposing action to that described earlier so that smooth muscle contracts once more. Blood flow into the penis diminishes and the subtunical veins are opened, allowing blood to escape again. The penis becomes flaccid.