Individual neurons containing prosomatostatin mRNA were identified with in situ hybridization histochemistry. Our results demonstrate a widespread distribution of prosomatostatin mRNA in several regions of the rat central nervous system. Neurons containing this transcript were most abundant in the anterior olfactory nucleus, hypothalamus, hippocampus, and amygdala as well as in all regions of the cerebral cortex. Moreover, the distribution of mRNA-containing perikarya was coextensive with the location of neurons containing somatostatin-like immunoreactivity in all areas of the brain examined. Somatostatin neurons varied in their morphology and amount of hybridization signal from region to region. The widespread distribution and regional variations in neuronal morphology and the amount of hybridization signal are consistent with a neurotransmitter and/or a neuromodulator role for somatostatin in addition to its well-established neuroendocrine role. These results demonstrate that both the peptide and its mRNA are found in perikarya in the same areas and that they are therefore the sites of synthesis for somatostatin.