The role of the pituitary, and in particular, of GH in GH-releasing hormone (GRH) gene expression was studied in hypophysectomized rats with and without GH treatment. Hypothalamic GRH mRNA was 6-fold greater in hypophysectomized than in control rats. Increased levels of GRH mRNA were observed at 3 days and the maximal increase was noted at 7 days, postoperatively. Administration of GH to hypox rats partially reversed the increase in GRH mRNA, suggesting a negative feedback regulation by GH of GRH gene activity at the transcript accumulation level. The overall regulation of GRH gene expression, however, appears more complex since GRH mRNA levels and GRH content exhibited discordant changes after both hypophysectomy and GH treatment, suggesting that factors other than GH are required for efficient translation of GRH mRNA.