1. Nitric oxide has potential anti-atherogenic actions as well as regulating vascular tone. Animal studies suggest that there are sex differences in basal nitric oxide biosynthesis, but it is not known whether such differences exist between men and women. 2. We have investigated this question by measuring forearm blood flow responses, using venous occlusion plethysmography, to brachial artery infusion of NG-monomethyl-L-arginine (an inhibitor of NO biosynthesis) and noradrenaline in 40 healthy subjects (20 men and 20 premenopausal women). Mean arterial blood pressure was 89 +/- 10 mmHg (mean +/- SD) in men and 87 +/- 9 mmHg in women, and mean total cholesterol was 4.25 +/- 0.99 mmol/l (mean +/- SD) and 4.26 +/- 0.80 mmol/l respectively. 3. In men, vasoconstrictor responses to NG-monomethyl-L-arginine, 1-4 mumol/min (15-28% mean reduction in blood flow), were consistently less than responses to noradrenaline, 60-240 pmol/min (26-37%), whereas in women, vasoconstrictor responses to NG-monomethyl-L-arginine (19-30%) were consistently greater than those to noradrenaline (11-17%). The sex difference in relative sensitivity to vasoconstrictors was significant (P < 0.001). 4. Our findings are consistent with either greater sensitivity to noradrenaline in men compared with premenopausal women, or a greater basal nitric oxide biosynthesis in premenopausal women compared with men.