Cyclic AMP was measured in both striatal slices and in the incubation medium after exposure to dopamine and dopamine antagonists. Dopamine increased cyclic AMP in both tissue and medium. The effect of dopamine was enhanced by sulpiride and domperidone, and to a lesser extent by haloperidol, but α-fluphenthixol had only an inhibitory effect. The enhancement by sulpiride was stereoselective and totally suppressed by the D 1 antagonist SCH 23390. Cyclic AMP in the medium provided the more sensitive measure of drug effect and increased linearly for up to 20 min., whereas the nucleotide in tissue remained stable or declined after 10 min. It is concluded that: (1) the increase in dopamine-stimulated cyclic AMP efflux caused by D 2 antagonists reflects increased intracellular cyclic AMP accumulation rather than an effect on the efflux mechanism; (2) dopamine enhances cyclic AMP accumulation via a D 1 a receptor, and simultaneously inhibits it through a D 2 receptor; and (3) changes in D 1 receptor-stimulated cyclic AMP formation in striatum may not be related to the clinical actions of neuroleptics. It remains possible that D 2 receptor-mediated inhibition of cyclic AMP accumulation stimulated by a different agonist system may underlie some of the therapeutic actions of dopamine agonists and antagonists