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The activity and regulatory properties of the adenylate cyclase system of the rat striatum were studied. Agents such as Gpp(NH)p, forskolin, and NaF were found to show classical in vitro stimulation of adenylate cyclase activity in the striatum membrane fraction. Dosage of rats with a preparation containing gangliosides (30 mg/kg, 6 i.p. injections) led to prolonged reductions in basal striatal adenylate cyclase activity. Two weeks after ganglioside administration, enzyme activity was reduced by 48% and remained lower than in controls (by 18%) even a month after injections. In vitro studies of the effects of gangliosides on adenylate cyclase activity in whole brain and striantal synaptosomes from rats showed that gangliosides have modulating actions on the adenylate cyclase system of the striatum, mainly due to changes in the catalytic function of the enzyme itself, and have no significant effect on the GTP-binding center of G-protein.