The comparative subcellular localization of the mRNAs encoding the stimulatory subunit of heterotrimeric G-proteins (G alpha s) and the vasopressin-secreted peptide was performed at the light and electron microscopic level. We find that although the G alpha s membrane protein is devoid of signal peptide sequence at its N-terminal extremity, its mRNA is aggregated on defined domains of the rough endoplasmic reticulum (RER). This suggests that the G alpha s protein is probably synthesized close to the RER, and that, on the pathway to the plasma membrane, this protein might be primarily associated with RER membranes. We further find that the mRNAs encoding the G alpha s membrane-attached protein and the secreted peptide vasopressin have different patterns of distribution within the neuronal perikarya. Overall, our results show that these two mRNAs are segregated to distinct domains of the RER. We speculate that the RER might be organized in specialized domains involved in distinct functions with respect to mRNA translation and/or protein postranslational modifications.