The site within the hypothalamic-pituitary axis at which cortisol acts to inhibit luteinizing hormone (LH) secretion was investigated in female pigs. Six ovariectomized, hypophysial stalk-transected (HST) gilts were given 1 microgram pulses of gonadotropin releasing-hormone (GnRH) iv every 45 min from day 0 to 12. On days 6-12, each of 3 gilts received either hydrocortisone acetate (HCA; 3.2 mg/kg body weight) or oil vehicle im at 12-hr intervals. Four ovariectomized, pituitary stalk-intact gilts served as controls and received HCA and pulses of 3.5% sodium citrate. Jugular blood was sampled daily and every 15 min for 5 hr on days 5 and 12. Treatment with HCA decreased serum LH concentrations and LH pulse frequency in stalk-intact animals. In contrast, serum LH concentrations, as well as the frequency and amplitude of LH pulses, were unaffected by HCA in HST gilts and were similar to those observed in oil-treated HST gilts. We suggest that chronically elevated concentrations of circulating cortisol inhibit LH secretion in pigs by acting at the level of the hypothalamus.