We have examined the effects of captopril on pressor responses to the selective alpha 1-adrenoceptor agonist cirazoline in the pithed rat preparation following treatment with phenoxybenzamine and/or nifedipine. Pretreatment with captopril reduced the pressor responses to cirazoline and displaced the dose-response curve for this agonist to the right, significantly increasing the ED50 without altering the maximum response. Pretreatment with phenoxybenzamine accentuated the inhibitory actions of captopril and a combination of phenoxybenzamine and captopril significantly increased the ED50 without altering the maximum response. Administration of nifedipine in animals, which had already received phenoxybenzamine and captopril, led to a further displacement to the right of the cirazoline dose-response curve. The ED50 was found to be significantly increased and the maximum response was now significantly depressed. Captopril produced further additive inhibition with nifedipine and phenoxybenzamine of the vasoconstrictor effects of cirazoline. These data indicate, perhaps not surprisingly, that the cellular basis for the inhibitory effects of captopril is different from that of nifedipine and phenoxybenzamine, however, more importantly, that captopril may directly, or indirectly, inhibit receptor-operated cation channel mediated pressor responses.