SYNOPSISThe interactions of four abortive anti‐migraine agents and four prophylactic anti‐migraine agents with 5‐HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti‐migraine agents (i.e. 5‐hydroxytryp‐tamine, ergotamine, dihydroergotamine, sumatriptan) for 5‐HT1D receptors range from 4.0 – 34 nM while the affinities of prophylactic anti‐migraine agents (i.e. methysergide, amitriptyline, (‐)propranolol, verapamil) range from 46 – 11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti‐migraine agents dose‐dependently inhibit forskolin‐stimulated adenylate cyclase activity, a biochemical effect mediated by 5‐HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti‐migraine agents. These date support the hypothesis that abortive anti‐migraine agents are 5‐HT1D receptor agonists and that this effect may underlie their anti‐migraine efficacy.