The mechanism whereby an increase in left atrial pressure (LAP) causes a water diuresis in the anesthetized dog remains controversial. In the present study LAP was increased by inflation of an atrial balloon in two groups of animals. In the first group of eight intact dogs, mean LAP was increased from 3.4 to 17.6 mm Hg (P less than 0.001). The rise in LAP was associated with a mean increase in urine flow (V) from 0.70 to 1.29 ml/min (P less than 0.001), a decrease in urinary osmolality (Uosm) from 808 to 490 mOsm/kg of H2O (P less than 0.001) and an increase in free water clearance (CH2O) from -0.684 to -0.200 ml/min (P less than 0.025). This diuresis was associated with a mean decrease in antidiuretic hormone concentrations in plasma as measured by radioimmunoassay from 27.6 to 12.3 pg/ml (P less than 0.02). The changes in the urinary indexes and in the antidiuretic hormone concentrations were reversible and returned to control levels when the LAP was allowed to return to normal. A second group of dogs was acutely hypophysectomized, steroid replaced and given a constant infusion of vasopressin. In these animals, mean LAP was increased from 3.0 to 16.0 mm Hg (P less than 0.001) but no significant change in V (0.49 to 0.56 ml/min), Uosm (878 to 845 mOsm/kg of H2O) or CH2O (-0.750 to -0.620 ml/min) occurred. Cardiac output, renal arterial pressure, glomerular filtration rate and solute excretion were comparable in the two groups. We therefore conclude that suppression of antidiuretic hormone release is the primary mechanism whereby increased LAP causes a water diuresis in the anesthetized dog.