There is evidence that D1 and D2 dopamine receptor subtypes coexist at the cellular level in the striatum and act synergistically to mediate the effects of dopamine. Other data suggest that these receptor subtypes are largely segregated in different striatal projection pathways. We used in situ hybridization in serial adjacent 4 microns sections to determine the extent of colocalization of D1 and D2 receptor mRNAs in rat striatal neurons. Cellular localization of D1 and D2 receptor mRNA was performed on section pairs that were hybridized with 35S-labeled cDNA or oligonucleotide probes directed against non-homologous regions of D1 and D2 receptor mRNAs. We found that 26-27% of striatal cells containing one receptor subtype also contained the other subtype. Thus, although D1 and D2 receptors are segregated in the majority of striatal neurons, a substantial number of striatal neurons coexpress both dopamine receptor mRNA subtypes. Our findings provide anatomic support for many of the functional interactions that have been described for D1 and D2 receptors.