The maternal circulation vasodilates during pregnancy. We investigated the contribution of nitric oxide to this vasodilatation. Using venous occlusion plethysmography, we measured the effect of nitric oxide synthase inhibition on hand blood flow during human pregnancy. We compared the response to a brachial artery infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) with the response to norepinephrine in three groups of women: nonpregnant, early pregnant (9-15 wk), and late pregnant (36-41 wk). Basal hand blood flow increased significantly during late pregnancy compared with nonpregnant and early pregnant subjects (P = 0.007). L-NMMA produced a greater reduction in hand blood flow in both pregnant groups compared with nonpregnant controls (P = 0.0003). Norepinephrine produced an attenuated response in late pregnancy compared with nonpregnant and early pregnant women (P = 0.0029). If other vascular beds respond in the same way as the hand, the gestational increase in vasoconstrictor response to L-NMMA that we observed implicates increased generation of nitric oxide in the fall of peripheral vascular resistance during healthy human pregnancy.