The peptidergic neurohormone somatostatin (SRIF) derives from a precursor called preprosomatostatin (PPS) by proteolysis. We have isolated by RT-PCR and sequenced a partial cDNA coding for the ovine PPS. It contains a 348 base pairs coding sequence that shares strong similarities with previously cloned mammalian cDNAs. The ovine cDNA was used to synthesize radiolabeled cRNA to probe the PPS mRNA in the ewe hypothalamus by in situ hybridization. The PPS mRNA-containing cells are widely distributed in the hypothalamus. According to the number of silver grains over a cell, they show various staining intensities. The distribution of the PPS mRNA is in good agreement with that of the peptide previously determined using immunohistochemistry. The strongest labeled areas include the periventricular region of the paraventricular nucleus and the lateral division of the ventromedial nucleus. The difference in labeling intensity observed in the diverse populations of labeled neurons could reflect various levels of neuronal activity.