The question which neurotransmitters mediate penile erection in humans is still unsettled. Although functional studies have established a role of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) in human penile smooth muscle relaxation, they did not allow a conclusion as to whether they are released by neurons or other cells. This article outlines the identification of numerous nitric oxide synthase (NOS) and VIP-containing axons in the human penis. More than 50% of the perivascular nerve fibres and more than 90% of the trabecular nerve fibres within the corpus cavernosum stained positive for both NOS and VIP. In contrast, endothelial cells stained only faintly for NOS-immunoreactivity, NOS/VIP-immunoreactivity was reduced (diabetes) or absent (lesion of the cavernous nerve) in penile tissue taken from patients with neurogenic impotence. These findings support the concept that NO and VIP act as neural comediators of penile erection in humans.