Isosmotic decreases in central venous pressure do not stimulate arginine vasopressin (AVP) secretion in normal humans, while symptomatic vasovagal hypotension produces large rises in plasma AVP levels. The effects of an asymptomatic fall in arterial pressure on plasma AVP in humans are poorly documented. Heart rate, mean arterial pressure, plasma osmolality, and plasma AVP were measured in seven healthy volunteers during infusion of sodium nitroprusside on two occasions, with and without central venous pressure measurements. On both study days, heart rate increases (5 ± 3 and 8 ± 4 beats/min) and mean arterial pressure reductions (12 ± 3 and 13 ± 2.0 mm Hg) were comparable. Plasma AVP (3.2 ± 1.4 and 4.0 ± 1.7 pg/ml at control) did not change on either study day after nitroprusside titration (30-40 minutes) or after an additional 90 minute observation on the first day. When measured on the second day, central venous pressure declined from 5.6 ± 1.9 to 2.9 ± 1.5 mm Hg, p < .001. Osmolality was constant on both days at all times. Unloading of sinoaortic baroreceptors produced by asymptomatic hypotension, coupled with a moderate reduction in central venous pressure, does not, therefore, stimulate plasma AVP secretion in normal humans. This observation has relevance to understanding the mechanisms involved in the reported increases in plasma AVP during orthostatic stress and in various diseases.