The effects of m-chlorophenylpiperazine (MCPP), a serotonin agonist, on spontaneous and evoked neural firing in nerves supplying the penis and bladder were examined in the urethan-anesthetized rat. MCPP (0.1-10 mg/kg iv) elicited, after a 2- to 4-min delay, an increase in spontaneous firing in cavernous nerves but no detectable firing in bladder nerves. The cavernous nerve firing was accompanied by an increase in intracavernous pressure and a depression of rhythmic bladder activity. Administration of ganglionic-blocking agents or transection of peripheral nerves revealed that the cavernous nerve discharge was mediated by activation of pre-ganglionic cholinergic pathways in the pelvic nerve. The effects of MCPP were noted in intact as well as in acute and chronic spinal rats and were prevented by the administration of the serotonin (5-HT) antagonist, metergoline (3 mg/kg im). These data indicate that pharmacological activation of 5-HT receptors, possibly of the 5-HT1B subtype, can facilitate the sacral preganglionic outflow to the penis and inhibit bladder activity.