We compared the effect of intracavernous administration of sodium nitroprusside, a nitric oxide donor and, therefore, stimulator of the cyclic guanosine monophosphate pathway, with the activity of prostaglandin E1, which is a stimulator of the cyclic adenosine monophosphate pathway. To date 105 patients with erectile dysfunction have entered the study. As part of the diagnostic evaluation every patient received an intracavernous injection of 20 micrograms prostaglandin E1 and a second injection of sodium nitroprusside at different concentrations (100 micrograms in 10 patients, 300 micrograms in 60 and 400 micrograms in 35). Sodium nitroprusside at a dose of 100 micrograms was not effective for inducing erections. Prostaglandin E1 induced better responses overall than sodium nitroprusside at 300 and 400 micrograms (p < 0.001). The overall duration of erections was also significantly longer with prostaglandin E1 (mean 88.5 minutes) than with 300 micrograms sodium nitroprusside (mean 50.8 minutes, p < 0.001) but did not reach statistical significance compared to 400 micrograms sodium nitroprusside (mean 42.2 minutes). Side effects were minimal with both drugs. Although sodium nitroprusside has several benefits over prostaglandin E1 for intracavernous use (such as lower cost, absence of local pain and shorter action, allowing detumescence after orgasm and decreasing the risk of priapism), prostaglandin E1 still remains the agent of choice for intracavernous use.