Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v. doses are 0.01-0.03 and 3-10 micrograms/kg or less, but increase in frequency, severity, and duration at higher doses. oCRH produces a biphasic plasma immunoreactive (IR)-ACTH response and has a prolonged duration of action that is probably due to its long circulating half-life. Other pro-opiomelanocortin IR-peptide are secreted concomitantly in equimolar amounts. Plasma IR-cortisol concentration tends to follow that of ACTH, but also reflects cortisol's longer circulating half-life and the fact that acutely the maximally-stimulating plasma IR-ACTH level is about 45 pg/ml. oCRH is as effective given s.c. as i.v., but intranasal administration is only 1% as effective. Sex and age have no effect on the plasma IR-ACTH and IR-cortisol responses to oCRH. The time of day of oCRH administration has little influence on the plasma IR-ACTH response, but the plasma IR-cortisol response is much greater to oCRH given later in the day than early in the morning. Plasma IR-ACTH response to oCRH is more dependent on the basal plasma IR-cortisol level than the time of day. Arginine vasopressin given at the same time as oCRH potentiates 4-fold the plasma IR-ACTH response to oCRH alone, almost to levels obtained with insulin-induced hypoglycemia. However, oCRH administered at the onset of insulin-induced hypoglycemia does not cause higher plasma IR-ACTH levels, indicating that endogenous CRH levels are maximally-stimulating during the hypoglycemic response.(ABSTRACT TRUNCATED AT 250 WORDS)