The effect of hypo- and hyperthyroidism on the plasma growth hormone (GH) response to synthetic human growth hormone releasing factor (GRF) was determined in conscious, freely moving rats pretreated with chlorpromazine and antiserum against somatostatin. Chlorpromazine plus somatostatin antiserum pretreated rats gave consistent response to GRF which was not observed in untreated rats. Chlorpromazine alone has no effect on GH secretion induced by GRF in rat pituitary monolayer culture. In rats made hypothyroid by thyroidectomy, both basal and peak plasma GH responses to a small (0.25 microgram/kg bw) and a moderate dose of GRF (1 microgram/kg bw) were significantly reduced as compared to controls. In rats made hyperthyroid by the administration of thyroxine, basal and peak plasma GH responses to a small but not to a moderate dose of GRF were significantly reduced as compared to controls. A reduced plasma GH response to a small dose of GRF was observed 8 days after the cessation of thyroxine administration. The pituitary GH reserve was markedly reduced in hypothyroid but not in hyperthyroid rats as compared to their respective controls. These results indicate that plasma GH response to GRF is reduced both in hypo- and hyperthyroidism. The mechanism involved in the phenomenon appears to be different between the two conditions.