Two studies were carried out to determine whether vasopressin influences the baroreceptor reflex of humans. In protocol 1, eight healthy subjects received sequential infusions of nitroprusside and phenylephrine to alter baroreceptor input. Muscle sympathetic nerve activity (SNA) was recorded to assess baroreceptor reflex modulation of efferent vasoconstrictor drive. Baroreceptor sensitivity (slopes) of the relationship between systolic pressure and R-R interval (cardiac baroslopes) and slopes relating muscle SNA to diastolic pressure were not altered during subpressor infusions of vasopressin, which raised basal plasma levels to 19 +/- 6 and 26 +/- 6 (mean +/- SE) pg/ml. A second protocol (n = 10 subjects) compared the reflex inhibition of SNA and heart rate produced by incremental pressor doses of phenylephrine and vasopressin. The calculated cardiac and sympathetic baroreflex gains did not differ between pressor agents. However, immediately following the peak dose of vasopressin (which elevated plasma levels to 35 +/- 3.6 pg/ml), reflex sympathoexcitation produced by unloading baroreceptors (with a bolus of nitroprusside) was significantly enhanced compared with an identical stress initiated at peak phenylephrine infusion. Thus increased levels of vasopressin ranging from 19 to 26 pg/ml did not alter cardiac or sympathetic baroreflex responses in humans. Higher levels of vasopressin may enhance the sympathetic response to unloading of baroreceptors.