The shaft of the penis is covered with normal skin, but the highly sensitive tip, the glans penis, is covered with thinner, more sensitive skin that is especially responsive to sexual stimulation. A fold of skin called the foreskin covers the glans of the human penis. The procedure known as circumcision removes a portion of the foreskin.

Sexual stimulation triggers responses in the nervous system that result in penile erection. Nerve endings release a neurotransmitter that causes the endothelial cells lining the penile blood vessels to release a gaseous neurotransmitter, nitric oxide (NO). NO diffuses into the smooth muscle cells that control the diameter of the penile arteries and stimulates them to produce the second messenger cGMP (see Figure 7.13). Increased cGMP in these muscle cells causes them to relax; the arteries dilate and carry more blood into the penis. Increased blood flow swells the shafts of spongy erectile tissue located along the length of the penis (see Figure 42.9). The enlargement of these blood-filled cavities compresses the vessels that carry blood out of the penis, and the erectile tissue becomes engorged with blood. The penis becomes hard and erect, facilitating its insertion into the vagina. Many species of mammals (though not humans) have a bone in the penis, but these species still depend on erectile tissue for copulation.

At the climax of copulation, 2 to 6 milliliters of semen are propelled through the vasa deferentia and the urethra in two steps, emission and ejaculation. During emission, rhythmic contractions of smooth muscles in the vasa deferentia and accessory glands move the semen into the urethra at the base of the penis. Ejaculation is caused by contractions of other muscles at the base of the penis surrounding the urethra. These contractions force the coagulum of semen through the urethra and out of the penis. The muscle contractions of ejaculation are accompanied by feelings of intense pleasure known as orgasm. They are also accompanied by transient increases in heart rate, blood pressure, breathing, pupil dilation, and skeletal muscle contractions throughout the body.

After ejaculation, NO release decreases and enzymes break down cGMP, causing the blood vessels flowing into the penis to constrict. The blood pressure in the erectile tissue decreases, relieving the compression of the blood vessels leaving the penis, and the erection declines.

Erectile dysfunction (ED), or impotence, is the inability to achieve or sustain an erection. ED may have different causes, including cardiovascular disease. Drugs used to treat ED act by inhibiting the enzyme that breaks down cGMP, thus enhancing the effect of NO released in the penis, which improves the ability to achieve and maintain an erection.