Trazodone, a non-tricyclic drug with antidepressant properties, diminished the central hypotensive response to clonidine in a dose-dependent manner. Both drugs were infused into the left vertebral artery of chloralose-anaesthetized cats. Intravenously injected trazodone did not reduce the central hypotensive effect of clonidine. The antagonism probably occurs at the level of central α-adrenoreceptors in the brain stem, where clonidine is the α-agonist and trazodone the α-antagonist. Such an antagonism, already known for clonidine and the tricyclic drugs also holds for non-tricyclic antidepressants, provided that they possess α-adrenoreceptor-blocking activity.