Metrazole (MTZ) induces sequential activation of c-fos, proenkephalin (Penk) and tyrosine hydroxylase (TH) gene expression in the rat adrenal and c-fos and Penk gene expression in the rat hippocampus. As in the rat, MTZ produced a dose-dependent induction of c-fos mRNA in the hamster adrenal and hippocampus together with an increase in adrenal TH mRNA. Although MTZ-induction of preproenkephalin (PPenk) mRNA was observed in the hippocampus of the hamster, the same treatment failed to induce PPenk mRNA in the hamster adrenal. These results indicate that Penk gene expression in the hamster is differentially regulated in the adrenal and hippocampus. Furthermore, the regulation of adrenal Penk gene expression differs significantly when rat and hamster are compared.