Cavernous smooth muscle relaxation is effected through a complex biochemical pathway; therefore, a defect in any step of this pathway may result in erectile dysfunction. Administration of pharmacologic agents which cause relaxation of the cavernous smooth muscle through a different mechanism may serve as an effective therapeutic alternative for impotent patients. To test this hypothesis two potassium channel openers, pinacidil and cromakalim, were used to initiate and maintain cavernous smooth muscle relaxation. The drugs were given as intracavernous injections in two animal models. In 10 dogs pinacidil and cromakalim produced full erection. With pinacidil (10(-2) M), the mean intracavernous pressure increased from a baseline pressure of 32.6 +/- 3.43 cm H2O to a peak intracavernous pressure of 131.8 +/- 12.01 cm H2O, and remained elevated for a period of 17.8 +/- 9.4 min. With cromakalim (10(-2) M) intracavernous pressure rose from a baseline pressure of 32 +/- 2.55 cm H2O to a peak intracavernous pressure of 140 +/- 3.39 cm H2O, for a period of 19.4 +/- 0.89 min. Additionally, in 5 primates injected with cromakalim (10(-2) M) intracavernous pressure rose from 24 +/- 3.81 to 131.2 +/- 7.56 cm H2O, for 27.0 +/- 4.79 min. It is concluded that both pinacidil and cromakalim can initiate and maintain erection in dogs and that cromakalim produces a similar erectile response in monkeys. Further study of the local and systemic effects of chronic injection is needed to determine whether this class of pharmacologic agents can provide therapy for impotent patients.