Neurons expressing immunoreactivity to antisera against somatostatin 14 and other somatostatin-related peptides were identified in the striatum of cats and nonhuman primates. In each species, immunoreactive neurons were distributed singly and in small groups in the caudate nucleus, putamen and ventral striatum. A detailed study was made of somatostatin-positive neurons and neuropil in the caudate nucleus of the cat. First, the mean diameters and surface areas of neurons expressing immunoreactivity to somatostatin 14 were made from peroxidase-antiperoxidase stained material. Second, fluorescence immunohistochemistry was combined with retrograde labeling of striatal neurons to determine whether such somatostatin 14-positive neurons emit axons projecting out of the striatum. Third, the distributions of neurons and neuropil expressing immunoreactivity to somatostatin 14 or somatostatin 28 (1-12) were plotted in relation to the locations of acetylcholinesterase-poor zones ("striosomes") visible in adjoining sections. The morphometric analysis suggested that somatostatin 14-positive neurons in the caudate nucleus form a single population of medium to medium-large neurons having mean diameters of 20 micron and mean surface areas of 154 micron2. The retrograde tracer study suggested that these somatostatin 14-positive neurons are interneurons. Injections of fast blue into all of the known targets of striatofugal fiber projections failed to label somatostatin 14-positive neurons save in a few instances (less than 0.3% of more than 4000 neurons) in each of which labeling was equivocal. Analysis of the distribution of somatostatin-positive neurons and neuropil in the striatum demonstrated that both observe striosomal ordering. Somatostatin immunoreactive neuropil was dense outside and weak inside identified striosomes, and most immunoreactive neurons lay outside. Often somatostatin-positive neurons lay beside, and sometimes striosomes partly rimmed them. The processes of such neurons tended to run along the borders of the striosomes without crossing them, but occasionally single processes and rarely entire dendritic trees crossed from one compartment to the other. These results suggest that, in the striatum of the cat, somatostatin is present: (1) in fibers organized according to the compartmental distribution already recognized for other neurochemical compounds in the striatum as well as for its afferent and efferent systems, and (2) in interneurons, mostly present in the extrastriosomal matrix, but also located near striosomes, where they could serve as interfaces between the striosomes and extrastriosomal matrix.