A double-blind, placebo-controlled clinical trial of the intracavernous injection of vasoactive intestinal peptide was conducted and studied in 24 men with erectile dysfunction of diabetic, neurogenic and psychogenic etiology. The patients were randomized into 6 groups of 4 subjects each and received either placebo, or 200 or 400 pmol. vasoactive intestinal peptide at each of 3 consecutive weekly visits. An increase in penile length was associated significantly with treatment (F equals 5.10, p equals 0.01), dose-related, and independent of the time and sequence of treatment. An increase in penile diameter was associated significantly with treatment (F equals 8.14, p equals 0.001) and time (F equals 8.14, p equals 0.001), dose-related and independent of the sequence of treatment. Penile rigidity was associated significantly with time (F equals 5.44, p equals 0.008), associated nearly significantly with treatment (F equals 3.11, p equals 0.056) and independent of sequence of treatment. Despite some measurable treatment-related increase none of the patients achieved penile rigidity adequate for intromission.