This study tested the hypothesis that gender affects the pressor and renal vasoconstrictor responses to angiotensin (Ang) I and Ang II in salt-replete normotensive subjects. Ang I and Ang II were infused in graded doses into 9 men and 8 women in a randomized, single-blind, crossover study. There were no differences between genders in baseline blood pressure, heart rate, sodium excretion, renal plasma flow, angiotensin-converting enzyme (ACE) genotype, ACE activity, plasma renin activity, aldosterone, or Ang II levels. Although pressor responses to Ang I and Ang II were similar in men and women, there was a negative relationship between the change in mean arterial pressure and the change in heart rate during Ang I and II infusion in women only. The half-time of the pressor response after discontinuation of Ang I but not Ang II infusion was greater in men than in women (9.5+/-2.2 versus 4.3+/-2.1 minutes, P<.05). This difference in duration did not result from gender differences in the metabolism of Ang I because Ang II levels measured during Ang I infusion were identical in men and women. In contrast, the renal vasoconstrictor response to Ang I and Ang II was significantly increased in women compared with that in men (Ang I, -243+/-31 versus -138+/-13 U/1.73 m2; Ang II, -233+/-25 versus -175+/-18 U/1.73 m2; P<.03). These data suggest an effect of gender on baroreflex reactivity during angiotensin infusion. Moreover, in the setting of similar Ang II concentrations, the dramatic difference in the renal vasoconstrictor responses to Ang I and Ang II between salt-replete men and salt-replete women suggests gender differences at a pharmacodynamic level.