In this work the ability of angiotensin II (AII) to potentiate the corticotropin-releasing activity of ovine CRF41 (CRF) and the intracellular mechanism responsible for this effect are described. In perfused rat anterior pituitary cells, AII (10(-8)M) was found to potentiate the corticotropin-releasing activity of CRF producing a parallel shift of the dose-response curve. Similar results for ACTH release were observed in monolayer cell cultures. In this system, the concentration of cAMP was measured and was shown to be increased in the presence of CRF with a maximal value (2.5-fold greater than control) after 5-10 min incubation. On the other hand, AII at a dose inducing ACTH release (10(-7)M), had no effect on basal cAMP concentration, but when given simultaneously with CRF, potentiated the CRF-induced cAMP production (1.9-fold greater than CRF value). These results indicate that AII potentiates the corticotropin-releasing activity of CRF and that this effect is preceded by a similar increase in the CRF-induced cAMP production.