The pituitary-adrenocortical response to ovine corticotropin-releasing factor (CRF) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) anesthetized with pentobarbital. After intravenous administration of various doses of CRF (0.1, 1.0 and 10 micrograms), the plasma levels of ACTH were significantly increased in both groups. ACTH increments after various doses of CRF were dose-dependent in WKY. ACTH increments after injections of 0.1, 1.0, and 10 micrograms of CRF in SHR were 123.2 +/- 36.5 (SE), 123.0 +/- 52.2 and 60.3 +/- 48.5 pg/ml at 5 min, and 386.3 +/- 73.8, 243.4 +/- 86.6 and 220.0 +/- 31.4 pg/ml at 15 min, respectively. The ACTH increments in SHR at 15 min after administration of 0.1 microgram of CRF were higher (p less than 0.02) than those in WKY. However, ACTH increments in SHR after administration of 10 micrograms of CRF were lower than those in WKY at 5 min (p less than 0.05) and 15 min. These data suggest that the plasma ACTH responses to various doses of CRF represent a dose-unrelated plateau response in SHR. The plasma levels of corticosterone after administration of various doses of CRF did not change significantly and there were no significant differences between the two strains. The results of these experiments suggest that SHR have an abnormal response of the pituitary-adrenocortical axis to CRF, and the abnormal response may be attributable to desensitization of the pituitary to CRF.