Excess production or long-term administration of glucocorticoids is detrimental to longitudinal growth in people and rats. A portion of this effect is attributed to cortisol inhibition of growth hormone (GH). Glucocorticoid effects are usually studied in subjects under long-term treatment with synthetic, more potent glucocorticoids, and, to the authors' knowledge, have not been examined in domestic animals. We sought to examine the effects of cortisol infusion on GH release in sheep. Cortisol infusion into castrated, male Suffolk sheep (1 to 1.5 years old) caused a significant (P < 0.0001) increase in cortisol concentration. Basal GH release was not affected over the 4-hour period of infusion. Growth hormone-releasing hormone administration stimulated GH release in both groups (P < 0.001); however, the control group had a greater response to growth hormone-releasing hormone than did the cortisol infused group (P < 0.0001). These results were duplicated in cultured sheep pituitary cells. Cortisol inhibition of GH release may be mediated via enhanced somatostatin release, owing to a direct inhibition of somatotrope function, or a combination of both mechanisms. Because of effects of stress and disease in increasing cortisol concentration, additional study of the mechanisms for cortisol inhibition of GH release in sheep needs to be performed.