1. We have determined in adrenalectomized male rats the effects of clamping plasma corticosterone and aldosterone at various concentrations on corticotropin-releasing hormone (CRH), neurotensin/neuromedin N (NT/N) and proenkephalin (pENK) mRNAs in the hypothalamus and amygdala using semi-quantitative in situ hybridization. 2. Corticosterone differentially regulated the levels of CRH and NT/N but not pENK mRNA. These effects were cell specific. CRH mRNA was reduced in the hypothalamic paraventricular nucleus (PVH), but increased in the central nucleus of the amygdala and bed nuclei of the stria terminalis. NT/N mRNA was never seen in the PVH, whereas levels increased in the central nucleus of the amygdala, but were unaffected in the lateral hypothalamic area. In those regions expressing pENK mRNA, levels were unaffected in all treatment groups. 3. CRH mRNA in both the central nucleus of the amygdala and PVH, and NT/N mRNA in the central nucleus of the amygdala were most sensitive to plasma corticosterone concentrations of less than 120 ng ml-1, i.e. those seen away from the peak of the diurnal rhythm. In adrenalectomized animals CRH mRNA in both the central nucleus of the amygdala and PVH could be set at levels usually seen in intact animals by the same plasma concentration of corticosterone. 4. The levels of CRH mRNA in the PVH and the central nucleus of the amygdala were closely correlated, while CRH and NT/N mRNA levels were similarly correlated in the central nucleus of the amygdala suggesting the existence of a common regulatory mechanism. The ED50 of their responses to corticosterone and correlations with thymus weight suggested the operation of glucocorticoid (type II) receptor mechanisms. 5. In the absence of corticosterone, aldosterone increased CRH and NT/N mRNA accumulation in the central nucleus of the amygdala, and increased CRH but not NT/N mRNA accumulation in the PVH. Aldosterone also blunted the dose-response effects of corticosterone on CRH and NT/N mRNA levels in the central nucleus of the amygdala, but not in the PVH. 6. These results suggest that, in intact animals, adrenal steroids play a major role in maintaining the levels of neuropeptide mRNAs in the PVH, bed nuclei of the stria terminalis and central nucleus of the amygdala. The results underscore the importance of cell-specific mechanisms operating to regulate the expression of neuropeptide genes in different cell types in response to diverse physiological conditions.