To understand the mechanisms of antianginal effects of trapidil, we examined the effects of trapidil, 100 mg i.v., on forearm veins and arteries in nine young healthy volunteers and compared the results with those of nitroglycerin, 0.3 mg s.1. At the doses used in the study, which are those in clinical use, trapidil and nitroglycerin increased forearm venous distensibility (p less than 0.05 for both) and decreased central venous pressure (CVP; p less than 0.01 for both). These results suggest that both drugs dilate veins. Forearm vascular resistance was decreased by trapidil but not by nitroglycerin. To examine the possibility that reflex vasoconstriction triggered by the decrease in CVP counteracted the direct vasodilator effect of the drugs, we studied the relationship between CVP and forearm vascular resistance while altering CVP by lower body negative pressure. Forearm vascular resistance at a comparable level of CVP was less after than before trapidil or nitroglycerin. These results suggest that both trapidil and nitroglycerin dilate forearm arteries in humans. Thus, we conclude that at a clinical dose, trapidil, as well as nitroglycerin, dilates forearm veins and arteries in humans.