Two groups of six healthy young males participated in separate experiments to examine the physiological role of endogenous vasopressin in h-CRH-induced (100 micrograms iv) ACTH release: a) after drinking of 3500 ml of water; b) after thirsting for 23 h; c) after 0.9% saline infusion, and d) after 5.0% saline infusion (0.06 ml/kg per min for 120 min). AVP levels were markedly elevated (4 ng/l) after thirsting and 5% saline infusion when compared with water loading or infusion of physiological saline. Although basal and h-CRH-stimulated ACTH and cortisol levels tended to be higher during hypertonic saline infusion and dehydration, no significant difference was observed between states of high or low endogenous AVP levels. These results are not in accordance with previous studies using ovine CRH, which might be due to its longer half-time or the timing of the changes in AVP plasma levels in relation to the CRH injection. Our data suggest that the osmotic modulation performed in this study results in AVP concentrations in the adenohypophysis, which are in the threshold range for influencing ACTH release induced by exogenous h-CRH.