I SHALL summarize very briefly some of the work which we ,have been doing in our laboratory relevant to the nature of the dopamine receptor and to the mechanism of action of neuroleptic drugs. Our involvement in the world of dopamine began with the superior cervical ganglion, and I’ll devote a small fraction of my presentation to summarize that work, which was carried out by MCAFEE, J. W. KEBABIAN and myself. We obtained evidencele3 suggesting that cyclic AMP mediates dopaminergic transmission in the ganglion and, thereby, modulates nicotinic cholinergic transmission through the ganglion. Part of the evidence that we had for this conclusion was the observation that dopamine, which was known to hyperpolarize the post ganglionic neurons of the ganglion, also causes an increase in ganglionic cyclic AMP. Moreover, we found that cyclic AMP is able to mimic the hyperpolarizing action of dopamine. The question as to how dopamine causes an increase in cyclic AMP was then studied, and it was found, using cell-free preparations of the ganglion, that dopamine stimulated an adenylate cyclase. This occurred at very low concentrations of dopamine, and the effect was specific for dopamine. These and other of our studies with the ganglion suggested that the “dopamine receptor” in the ganglion was the dopamine-binding portion of a dopamine-sensitive adenylate cyclase, and that this enzyme might be involved in the mediation of dopaminergic synaptic transmission in the ganglion. In view of the work of HORNYKIEWICZ, CARLSSON and their collaborators, as well as of a number of other investigators, we turned our attention to the dopamine receptor of the caudate nucleus, with the idea that possibly this dopamine receptor, which had been well characterized pharmacologically, both in intact experimental animals and clinically, might, like the dopamine receptor in the ganglion, be the dopamine-binding portion of a dopamine-sensitive adenylate cyclase. To test that possibility, KEBABIAN, PETZOLD and I prepared homogenates of caudate nuclei of the rat, and examined the homogenates for the presence of dopamine-sensitive adenylate cyclase activity.4 There was, indeed, such an adenylate cyclase in the caudate nucleus, and interestingly, virtually all of the known properties of the caudate dopamine receptor could be mimicked by the properties of this cell-free enzyme system. For instance, this adenylate cyclase was stimulated by very low concentrations of dopamine (Fig. 1). (Norepinephrine was considerably less effective than dopamine in stimulating enzyme activity, and isoproteronol was virtually ineffective.) The stimulatory effect of dopamine was mimicked by very low concentrations of apomorphine (Fig. 2). The stimulatory effect of either dopamine or apomorphine was prevented