Isolated arteries and veins from the hand and mesentery of healthy human subjects were studied in vitro. Serotonin caused contraction with an intrinsic activity approximately equal to that of norepinephrine and epinephrine in mesenteric and hand arteries and veins. Ketanserin inhibited the response to serotonin in a competitive, probably partly irreversible manner in the mesenteric vessels and the hand arteries. In the hand veins, ketanserin counteracted the serotonin-induced contraction in a noncompetitive way.