Cardiovascular and sympatho-adrenal responses to a reproducible mental stress test were investigated in eight healthy young men, before and during intravenous infusion of the NO synthesis inhibitor L-NMMA. Before L-NMMA the stress responses included significant increases in heart rate, mean arterial pressure and cardiac output, and decreases in systemic vascular resistance and in forearm vascular resistance. Arterial plasma norepinephrine increased. At rest after 30 min of intravenous infusion of L-NMMA (0.3 mg/kg/min), mean arterial pressure increased from 98±4 to 108±3 mm Hg (p<0.001), due to an increase in systemic vascular resistance from 12.9±0.5 to 18.5±0.9 U (p<0.001). Cardiac output decreased from 7.7±0.4 to 5.9±0.3 L/min (p<0.01). Arterial plasma norepinephrine decreased from 2.08±0.16 to 1.47±0.14 nmol/L. Repeated mental stress during continued infusion of LNMMA (0.15 mg/kg/min) induced qualitatively similar cardiovascular responses, but there was a marked attenuation of the increase in mean arterial blood pressure, resulting in similar "steady state" blood pressures during mental stress without and with NO blockade. Increases in heart rate and cardiac output were attenuated, but the stress-induced decreases in systemic and forearm vascular resistances were essentially unchanged. Arterial plasma norepinephrine increased less than during the first stress test. Thus, the increased arterial tone at rest during L-NMMA infusion is compensated for by attenuated increases in blood pressure during mental stress, mainly through a markedly attenuated cardiac output response, and suppressed sympathetic nerve activity.