These studies compared the relative potencies of CRF and arginine vasopressin (AVP) as ACTH secretagogues in the sheep. Dose-response curves to CRF (10, 25, 50, and 100 micrograms/h) and AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h) were obtained in five adult sheep, with arterial blood samples taken for CRF, AVP, ACTH, and cortisol measurements to determine the pituitary-adrenal response. It was found that the first dose of CRF increased plasma CRF levels to 444 +/- 79 pg/ml. ACTH levels rose significantly from 28 +/- 5 to 186 +/- 46 pg/ml, with a concurrent rise in cortisol levels from 7 +/- 3 to 44 +/- 9 ng/ml. Although plasma ACTH and cortisol levels remained elevated, higher doses of CRF failed to produce further increases. AVP, at all of the doses studied, did not produce an increase in ACTH levels, although cortisol levels rose significantly by the second dose. In a second series of experiments, animals received a continuous infusion of CRF (10 micrograms/h) alone or in combination with graded doses of AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h for 60 min each). It was found that AVP at the highest dose was able to potentiate the ACTH response to CRF. Lower doses of AVP, which did not stimulate a further increase in ACTH levels were, however, associated with a significant rise in cortisol levels. In conclusion, it was found that although CRF alone was a potent stimulator of ACTH secretion, AVP at the doses studied was not able to elicit an ACTH response in the conscious intact sheep. However, a dose of AVP that was not stimulatory in itself was able to augment the ACTH response to CRF.