It is well known that chronic supraphysiological doses of glucocorticoids (GC) inhibit GH secretion in vivo, and stimulate GH secretion from the somatotropes in vitro. It has been suggested that GC exert an inhibitory role in the hypothalamus surpassing the GC-positive effect at the somatotrope level. To test the hypothesis that GC can affect growth hormone-releasing releasing factor (GRF) and somatostatin (SS) at the hypothalamic level, we studied the effect of corticosterone on the immunoreactive content of GRF (IR-GRF) and SS (IR-SS) in cells and media of fetal hypothalamic cells in culture. After 20 days in culture, cells were incubated with serum-free medium containing corticosterone (from 0.3 to 300 nM) for 48 h. Corticosterone had a dual effect on IR-GRF. Concentrations in the range of the glucocorticoid receptor Kd (3 nM) increased peptide content, whereas higher concentrations (30 and 300 nM) decreased IR-GRF content in cells and media. Conversely, corticosterone increased SS cell content, only at a concentration of 3 nM, inducing a 2- to 3-fold increment in media content with the highest doses (30 and 300 nM). These results demonstrated that both GRF and SS are modulated by corticosterone in primary fetal rat hypothalamic cultures. Whereas GRF exhibited a dual response, stimulatory and inhibitory, at low and high corticosterone doses, respectively, SS showed a parallel increase with the corticosterone concentrations.