In the sheep cerebral vasculature 5-hydroxytryptamine (5-HT) caused a contraction of which ketanserin was found to be an effective antagonist (Basilar artery, pA2 = 9.33 +/- 0.16; middle cerebral artery, pA2 = 9.19 +/- 0.16; pial artery, pA2 = 9.47 +/- 0.12). Sumatriptan (GR 43175), a selective 5-HT1-like receptor agonist, was also found to have a small contractile effect on the sheep cerebral vasculature (Basilar artery, pD2 = 6.26 +/- 0.11; middle cerebral artery, pD2 = 6.25 +/- 0.10; pial artery, pD2 = 6.13 +/- 0.15). The contractile effect of sumatriptan was not antagonised by either ketanserin (1 microM) or MDL 72222 (1 microM). 5-HT therefore appears to cause contraction by stimulation of a mixed receptor population of 5-HT1-like and 5-HT2 receptors. In the sheep middle cerebral artery the addition of haemolysate was found to cause a contractile response and also to augment the contractile effects of both noradrenaline and 5-HT but only in the presence of a functional endothelium. However, 5-HT was never found to relax precontracted rings of the middle cerebral artery in either the presence or absence of a functional endothelium. These results indicate a basal release of EDRF in cerebral arteries that attenuates the effects of various constrictor agents.