The present study documents the existence in mammalian brain of a phosphoprotein which may play a biological role in dopaminoceptive neurons. This protein has been designated DARPP-32 (dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000). The regional distribution of DARPP-32 in the rat brain follows the general pattern of dopaminergic innervation. DARPP-32 is present in dopaminoceptive rather than dopaminergic neurons. Moreover, it appears to be concentrated in a subpopulation of dopaminoceptive cells, namely those containing D-1 receptors (dopamine receptors coupled to adenylate cyclase activation), where it is localized in cell bodies, dendrites, axons, and nerve terminals. DARPP-32 is phosphorylated in intact cells from the caudatoputamen by dopamine and by 8-bromo-cyclic adenosine 3':5'-monophosphate and in cell-free preparations by cyclic adenosine 3':5'-monophosphate-dependent protein kinase. In two accompanying papers, we report the purification and biochemical characterization of DARPP-32 (Hemmings, H.C., Jr., A.C. Nairn, D.W. Aswad, and P. Greengard (1984) J. Neurosci. 4: 99-110) and the immunocytochemical localization of this phosphoprotein (Ouimet, C.C., P. Miller, H.C. Hemmings, Jr., S.I. Walaas, and P. Greengard (1984) J. Neurosci. 4: 111-124).