The effects of several drugs usually considered as serotonin (5HT) -antagonists were studied in a model of the external carotid circulation, the canine nasal vascular bed. 1. It was confirmed that 5-HT constricts this vascular bed but that after administration of a large dose of ergotamine (10–2 mg/kg i.v.), 5-HT dilates the nasal vessels. 2. All drugs studied (Org GB 94, Org GC 94, ergotamine, dihydroergotamine, methysergide, pizotifen, cyproheptadine and clonidine) at relatively low concentrations can potentiate 5-HT induced vasoconstriction. 3. At higher doses of these drugs the 5-HT response is inhibited.4. The vasodilator response to 5-HT obtained in erotamine-treated dogs is inhibited by all other agents investigated.