When administered to mice pretreated with the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, the preferential autoreceptor antagonists (+)-AJ76 and (+)-UH 232 induced weak locomotor stimulation. When either (+)-AJ 76 or (+)-UH 232 was combined with a subthreshold dose of the selective NMDA antagonist dizocilpine (MK-801), a marked locomotor stimulation was produced in monoamine-depleted mice. The mechanism of this stimulation, although reduced by dopamine antagonists, remains to be clarified.