In isolated human mesenteric and crural veins, ergotamine induced long-lasting contractions. These contractions were resistant to repeated wash-out and were not affected by alpha-adrenoceptor blockade, but could be abolished by removal of extracellular calcium or by the presence of the calcium-blocker nifedipine. In contrast to its effect on human mesenteric and crural veins, ergotamine had no contractile effect, but a marked relaxant effect on mesenteric arteries mediated via blockade of alpha-receptors. The ergotamine-induced contraction was not affected by indomethacin (0.28--2.8 microM) nor was it influenced by serotonin (5-HT). In both mesenteric and crural veins, the ergotamine-induced contraction was diminished by the 5-HT blocking agent, methysergide. In veins, development of tachyphylaxis to 5-HT was demonstrated. It is concluded that ergotamine has a direct contractile effect on isolated human mesenteric and crural veins. These effects are dependent on unhindered influx of extracellular calcium and are at least partly mediated via 5-HT receptors. In mesenteric arteries, ergotamine acted as an alpha-adrenoceptor blocker, and had no contractant effect.