We examined the funetional significance of the presynaptic alphaadrenergic receptor, inhibitory to stimulus-induced norepinephrine release. The effects of prazosin and phentolamine. alpha-adrenergic receptor antagonists with different in vitro selectivities for the presynaptic alpha-receptor. on mean arterial pressure and serum renin activity were determined in the conscious rat. Both drugs resulted in dose-related reductions in mean arterial pressure and dose-related increases in heart rate and serum renin activity. However, consistent with the greater selectivity of prazosin for the postsynaptic alpha-receptor, a given reduction in arterial pressure was associated with a lesser increment in heart rate and serum renin activity after prazosin than after the nonselective agent phentolamine. The differential effects of these agents on heart rate and serum renin activity are consistent with different degrees of blockade of a functionally significant presynaptic alpha-receptor.