Recent in vitro and in vivo studies have suggested that nitric oxide may be the neurotransmitter responsible for cavernous smooth muscle relaxation and penile erection. Sodium nitroprusside, after combining with different kinds of thiols in the cellular cytoplasm, can effect nitric oxide release. We undertook this study to determine the physiologic response to sodium nitroprusside injection when used to induce and maintain penile erection in three species. Sodium nitroprusside was injected in increasing concentrations into the cavernous tissue of rats, dogs and monkeys. Dosages injected were 10(-4) M, 10(-3) M and 10(-2) M in 10 rats; 10(-4) and 10(-3) M in five dogs and five monkeys. The volume of drug injected was 0.05 ml for the rats and 0.5 ml for dogs and monkeys. The results show a dose-dependent erectile response to sodium nitroprusside injection (mean intracavernous pressure increase of 102.4 cm H2O in dogs, and 98.4 cm H2O in monkeys after injection of 10(-3) M nitroprusside). However, only a slight increase in intracavernous pressure (mean increase 28.4 cm H2O after injection of 10(-2) M of sodium nitroprusside) was noted in rats. The drop in blood pressure was > 15 mmHg in dogs and monkeys, while in rats it varied according to the dose studied. Sodium nitroprusside induced excellent erections in dogs and monkeys with minimal alteration in blood pressure. However, administration in rats resulted in hypotension. Nitroprusside may not be an acceptable nitric oxide donor for the treatment of male erectile dysfunction.