The effect of intra-arterial histamine on fingertip blood flow (FBF) and vascular resistance (FVR) was studied in normal subjects during reflex sympathetic vascoconstriction induced by body cooling and vasoconstriction caused by intra-arterial noradrenaline. In a room at 20 degrees C, FBF increased from 15.3 +/- 35.5 (SD) to 28.3 +/- 55.9 ml min-1 100 ml-1 of tissue and FVR decreased from 23.7 +/- 17.7 to 11.9 +/- 9.9 mmHg X ml min-1 100 ml-1 (P less than 0.01) during infusions of histamine (0.5-4 micrograms/min) in 14 subjects. In nine of these subjects, the disappearance half times of local injections of Na131I were measured and decreased from 19.8 +/- 10.9 to 12.9 +/- 7.3 min during histamine infusions, indicating an increase in nutritional flow. Arteriovenous shunt flow was also probably affected, for increases in FBF were sometimes large and FBF increased without a change in the radioisotope half time in two subjects. Neither cimetidine nor pyrilamine (mepyramine) consistently prevented the FBF responses to histamine. Administration of both antihistamines together attenuated the response. During noradrenaline infusions in four subjects, a large increase in FBF (8.9 +/- 10.9 to 39.0 +/- 8.2 ml, P less than 0.005) occurred at the smallest dose (0.5 micrograms/min) of histamine. It is concluded that histamine can vasodilate fingertips and increase nutritional blood flow during reflex sympathetic vasoconstriction. This vasodilatation may be mediated via both histamine H1 and H2 receptors.