Previous studies have reported that the mRNAs encoding the cloned mu-opioid receptor (MOR1) and the cloned delta-opioid receptor (DOR1) are expressed in the dorsal root ganglia (DRG) of rats. In the present study, we determined the sizes of DRG neurons expressing DOR1 and MOR1 mRNAs and examined whether or not DRG neurons were likely to be the source of the DOR1 and MOR1 immunoreactivity previously observed in the spinal dorsal horn. DRG neurons were labeled in five male Sprague-Dawley rats by applying Fluoro-Gold (FG) topically to the dorsal root entry zone. Five-micrometer cryostat sections were cut, and in situ hybridization was performed using full-length cRNA probes labeled with 35S-UTP. The distribution of sizes of DRG neuronal profiles (1372 neuronal profiles were evaluated) ranged from 98 to 2081 microm(2) and was similar to those found in previous reports. Of 583 retrogradely labeled neuronal profiles in DRGs, 246 (40 +/- 14%, mean +/- SD, n = 5) expressed MOR1 mRNA. Of 789 DRG cell profiles from sections that were hybridized for DOR1 mRNA, 687 (85 +/- 18%, mean +/- SD, n = 5) were labeled for DOR1. The proportion of DRG cell profiles expressing DOR1 mRNA was significantly higher than that expressing MOR1 mRNA (P < 0.0001, chi-square test). No significant differences were observed between small (less than or = 700 microm(2)) and large (> 700 microm(2)) FG-labeled neurons in the proportions labeled for either MOR1 mRNA (202/497 vs. 44/86, P > 0.2, chi-square test) or DOR1 mRNA (555/651 vs. 132/138, P > 0.3, chi-square test). Most FG-labeled neurons that expressed either MOR1 mRNA or DOR1 mRNA (82.1 and 80.8%, respectively) were smaller than 700 microm(2). In addition to cells expressing a single opioid receptor, individual DRG neurons were observed that expressed both MOR1 and DOR1. In a sample of 25 DRG neurons expressing MOR1-mRNA, 23 also expressed DOR1 mRNA. Within the spinal cord itself, DOR1 and MOR1 mRNAs had different patterns of expression. Both were expressed in the dorsal horn, but of the two, only MOR1 message was expressed in the superficial dorsal horn. We conclude that both small and large DRG neurons express DOR1 and MOR1 mRNAs, but most cells expressing these mRNAs are small. In addition, some DRG neurons express both MOR1 and DOR1 mRNAs. Finally, both DOR1 and MOR1 in the spinal dorsal horn originate, at least in part, from DRG neurons.