Effect of lisuride, an ergot derivative of isolysergic structure, on dopamine-sensitive adenylate cyclase was studied in the homogenate of rat corpus striatum. Stimulatory action of lisuride, similar to the actions of dopamine and apomorphine, on striatal adenylate cyclase was potentiated significantly by guanosine triphosphate (GTP) and by guanyl-5'-yl imidodiphosphate (GMP-PNP), although with lisuride alone, there was only a slight stimulation. The maximal stimulation attained in the presence of GTP corresponded to about 1.4 times the basal rate of cyclic AMP formation in the homogenate and was abolished by an addition of haloperidol. Lisuride at a concentration about 3 microM inhibited stimulation of cyclic AMP formation by dopamine. The effect of lisuride and the extent of potentiation by the guanyl nucleotides were almost comparable to the effects of apomorphine, under corresponding conditions. Thus, lisuride, like apomorphine, acts as a partial agonist-antagonist, and has the ability to stimulate the dopamine-sensitive adenylate cyclase in the rat corpus striatum.