5-Hydroxytryptamine (5-HT) elicited concentration-dependent contractions of the rabbit isolated saphenous vein. The effects of 5-HT were mimicked by 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3-(l,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969) and sumatriptan; the rank order of potency (pD 2 values) was 5-CT (7.6) > 5-HT (6.9) > 8-OH-DPAT (6.2) > RU 24969 (6.1) > sumatriptan (5.7). The maximal response to RU 24969 was less than that to the other compounds, implying that RU 24969 may behave as a partial agonist. Methiothepin (10 −8, 3 · 10 −8 and 3 · 10 −7 M). ketanserin (10 −7, 3 · 10 −7 and 10 −6 M) and spiperone (10 −7, 10 −6 and 10 −5 M), but not laH,3α,5αH-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222; 10 −7, 10 −6 or 10 −6 M), cyanopindolol (10 −7 and 10 −6 M) or propranolol (10 −7 and 10 −6 M), shifted the concentration-effect curve of 5-HT to the right in a concentration-dependent manner with pA 2 values of 8.25, 7.51 and 6.12, respectively. The high activity of 5-CT and methiothepin compared to, respectively. 5-HT and ketanserin (and spiperone) suggests that the contraction of the rabbit saphenous vein is not mediated by 5-HT 2 receptors. The receptor involved seems to be mainly 5-HT 1-like, similar to the one mediating contraction of the dog saphenous vein, human basilar artery and porcine cranial arteriovenous anastomoses.