The cellular distribution of guanylate cyclase (EC 4.6.1.2), guanosine 3′,5′-phosphate (cyclic GMP), cyclic GMP-dependent protein kinase (EC 2.7.1.38), and cyclic GMP phosphodiesterase (EC 3.1.4.17) have been examined in the rostral rat caudate-putamen complex. Immunofluorescent staining for guanylate cyclase, cyclic GMP, and cyclic GMP-dependent protein kinase in fresh frozen caudateputamen tissues is analogous to the immunoperoxidase localization in perfusion-fixed striatal slices. Homologous immunoreactivity in the cytoplasm and processes of ovoid and rounded neurons, 15–20 μm in diameter can be seen for these three components of the cyclic GMP system. Immunoreactive neurons are uniformly distributed throughout the caudate-putamen complex of all experimental tissue examined. Occasional large neurons, greater than 25 μm in diameter, in the ventral region of the striatum show immunoreactivity. Enzyme histochemical determination of the activities of guanylate cyclase and cyclic GMP phosphodiesterase show the medium-sized neuronal population (15–20 μm) contain hydrolytic activity for these proteins. Large- to medium-sized capillaries demonstrate guanylate cyclase synthetic activity, but the endothelial cells do not exhibit immunohistochemical staining. This suggests that physiological activity of an enzyme cannot be completely discerned through application of immunohistochemical procedures. Additionally, enzymatically detected guanylate cyclase histochemical activity was not uniformly distributed throughout the striatal neuropil. Enzyme histochemical detection of cyclic GMP phosphodiesterase demonstrates homologous cellular staining to guanylate cyclase enzymatic reactivity. The activity of the phosphodiesterase hydrolytic enzyme could be detected evenly distributed throughout the neuropil within cells 15–20 μm in diameter, analogous in cytoarchitecture to immunohistochemically visualized guanylate cyclase, cyclic GMP, and protein kinase elements. Ultrastructural examination of rat caudate-putamen demonstrates that the immunoreactivity for the components of the cyclic GMP system is predominantly distributed within the medium-spiny neuron subtype of this structure. Occasional aspiny neurons demonstrate peroxidase immunoreactivity for the cyclase, cyclic GMP, and the protein kinase, as does the luminal surface of capillary endothelial cells. The subcellular distribution of the antigenic determinants for these three elements and the hydrolytic activity of the phosphodiesterase enzyme show proximity to one another and are confined to the postsynaptic region of asymmetrical, but not symmetrical, terminal boutons. The asymmetrical terminal population of the caudate-putamen is derived from striatal afferents from the neocortex, intralaminar thalamus, and substantia nigra, and to a lesser extent the intrinsic striatal circuitry. The localization of four components of the cyclic GMP system within homologous subcellular components, showing proximity to one another and to the active region of the synapse, suggests that the cyclic GMP system has a function in neural communication in the rat caudate-putamen.