The distributions of messenger RNAs encoding both the D1 and D2 dopamine receptors have been determined in the rat brain by in situ hybridization. High levels of both mRNAs were found in the traditional dopaminoceptive regions of brain, including the caudate-putamen, nucleus accumbens, and olfactory tubercle; lower levels of both were found in a number of other neural structures, such as the lateral septum, olfactory bulb, hypothalamus, and cortex. High levels of D2 but not D1 receptor mRNA were identified in the midbrain dopamine cell groups, suggesting that the autoreceptors found in the substantia nigra and ventral tegmental area are exclusively D2. Other areas demonstrating differential distribution of these two mRNAs included the pituitary, amygdala, and hippocampus. Quantitative densitometric analysis revealed that in most of the brain regions studied in which both messages exist, the amounts of D1 and D2 receptor mRNAs were approximately equal. Finally, using thin (2.5-micron) sections through the caudate-putamen, about half of all cells were found to be positive for D1 receptor mRNA, and approximately 75% of cells contained D2 receptor mRNA. Subsequent analysis in sequential sections revealed that co-localization of D1 and D2 receptor mRNA occurred in 33% +/- 7% of all caudate-putamen cells: about half of all cells containing D1 receptor mRNA also contained D2 receptor mRNA, and approximately half of all D2 receptor mRNA-positive cells also contained D1 receptor mRNA. These results indicate that there is considerable overlap between D1 and D2 dopaminoceptive cells, and provide a basis for future regulatory studies of dopamine systems in brain within a defined anatomic context.