The distribution of dopamine D-1 receptors has been determined in the rat brain by a quantitative in vitro light-microscopic autoradiographic method. The binding of [N-methyl-3H]-SCH 23390 to slide-mounted tissue sections takes place with characteristics expected of a substance that recognizes D-1 receptors. The binding is saturable, has high affinity, and exhibits an appropriate pharmacology and stereospecificity in several discrete microscopic brain regions as determined by quantitative autoradiography. The highest density of D-1 receptors occurs in the caudate-putamen, accumbens nucleus, olfactory tubercle, and the substantia nigra pars reticulata. High concentrations of D-1 receptors were associated with the intercalated and medial nuclei of the amygdala, entopeduncular nucleus, and major island of Calleja. Furthermore, moderate to low concentrations were observed in several other structures, such as the frontal cortex, subthalamic nucleus, and several thalamic, hypothalamic, and hippocampal areas. The distribution of D-1 receptors correlates very well with projection areas of dopaminergic pathways. This technique furnishes a powerful assay for the accumulation of detailed pharmacologic and anatomical data about D-1 receptors, and the results suggest possible CNS sites of action of D-1 dopamine receptor selective compounds.