Studies were performed in anesthetized dogs to investigate the mechanism of the suppression of vasopressin and adrenocorticotropic hormone (ACTH) secretion by clonidine. Injection of clonidine (30 micrograms/kg i.v.) produced an initial increase in arterial pressure followed by hypotension, decreased heart rate, increased right atrial pressure and decreased plasma renin activity. Plasma vasopressin concentration decreased from 14.6 +/- 3.0 to 2.2 +/- 0.4 pg/ml (P less than .01), and this was accompanied by increases in urine volume and free water clearance from 0.15 +/- 0.02 to 1.03 +/- 0.28 and -0.50 +/- 0.05 to 0.30 +/- 0.27 ml/min, respectively (P less than .01), and a decrease in urinary osmolality from 1450 +/- 124 to 372 +/- 97 mOsmol/kg of H2O (P less than .01). Plasma corticosteroid concentration, used an an index of ACTH secretion, decreased from 8.9 +/- 1.6 to 2.2 +/- 0.3 micrograms/dl (P less than .01). Plasma osmolality did not change. Pretreatment of dogs with the alpha adrenoceptor antagonist yohimbine (2 mg/kg i.p.) blocked all cardiovascular, endocrine and renal responses to clonidine. Bilateral cervical vagotomy did not block the suppression of vasopressin or corticosteroid secretion by clonidine. Intraventricular injection of yohimbine blocked the hypotension and suppression of plasma corticosteroid concentration produced by clonidine but did not block the decrease in plasma vasopressin concentration or the associated renal effects of clonidine. Intracarotid infusion of clonidine caused small decreases in plasma vasopressin and corticosteroid concentrations even though blood pressure decreased by 22 mm Hg. Intraventricular and intravertebral clonidine had no significant effect on plasma vasopressin or corticosteroid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)