The present study investigated whether or not the beta-sympathomimetic amine isoprenaline, given systemically to conscious rats, influences corticotrophin (ACTH) release and if so, what could be the role of vasopressin in this response. Isoprenaline (i.m.) elevated plasma ACTH-like immunoreactivity (ACTHi) in a time- and dose-dependent manner. The highest dose of isoprenaline used (240 microgram/kg) raised plasma ACTHi about six fold. Most of the ACTHi co-migrated with porcine ACTH-(1-39) on Sephadex G-50 column chromatography. The beta-receptor antagonist propranolol abolished the increase in plasma ACTHi induced by isoprenaline, as did dexamethasone pretreatment. The increase in plasma ACTHi following isoprenaline (120 microgram/kg) injection was diminished by about 35% in rats congenitally lacking vasopressin (Brattleboro rats), when compared to normal rats. The vasopressin analogue, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]-arginine-vasopressin, almost completely prevented the rise in plasma ACTHi provoked by i.v. injection of arginine vasopressin and diminished by about 40% the isoprenaline-(120 microgram/kg)-caused ACTHi release. However, this vasopressin analogue had no effect in Brattleboro rats. These results indicate that isoprenaline, given systemically, stimulates the release of pituitary ACTH and this response appears to be mediated in part by vasopressin acting as an ACTH-releasing factor.