This study evaluated with electrophysiological and behavioral techniques the ability of rimcazole, a novel putative antipsychotic and selective sigma-receptor ligand, to antagonize the stimulation of the mesocorticolimbic dopamine system by the sigma-agonist, (+)SKF 10,047. Rimcazole effectively blocked the (+)SKF 10,047-induced excitation of ventral tegmental dopamine neurons while having no effect on either spontaneous activity or apomorphine-elicited slowing of A10 firing. Rimcazole also antagonized the behavioral hyperactivity produced by (+)SKF 10,047, but not by d-amphetamine which is also mediated through the same mesolimbic dopamine pathway. These data provide further evidence that rimcazole's novel pharmacologic profile may involve a blockade of sigma-receptors on mesocorticolimbic dopamine neurons.