Changes in tension were monitored isometrically on helical strips from both femoral and saphenous human veins obtained during autopsy and during surgical removal of varicose veins respectively. Both venous tissues contracted in response to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). While 5-HT was about 2 times more potent in saphenous (pD2 = 7.35) than in femoral veins (pD2 = 7.04), 5-CT stimulated the saphenous vein (pD2 = 7.62) at about 20 times lower concentrations than were required for stimulation of the femoral vein (pD2 = 6.27). 8-OH-DPAT induced venoconstriction only when used at very high concentrations and pD2 values could not be determined. These data suggested different subtypes and/or distribution of 5-HT receptors in both venous preparations. Further evidence for this was obtained by the observation that spiperone (a 5-HT receptor blocker with high affinity for 5-HT2 and 5-HT1A sites) produced a parallel shift to the right of the 5-HT curve in femoral veins but elicited a biphasic displacement of the 5-HT curve in saphenous veins. In the femoral vein, spiperone showed a pA2 value of 9.20 +/- 0.08, statistically not different from that calculated for the spiperone sensitive 5-HT effect in saphenous vein (pA2 = 9.14 +/- 0.08). The results suggest that regional variations in the distribution of 5-HT receptor subtypes do exist, human femoral veins possessing mainly 5-HT2 receptors whereas in human saphenous veins both 5-HT1-like and 5-HT2 receptors are present.