Acute hypoxia elicits diuresis, natriuresis, and hypotension in many mammalian species, but the cause of this effect remains unclear. The present study, using chronically instrumented rats, was undertaken to assess a possible role of atrial natriuretic factor (ANF) in these hypoxic responses. Acute hypoxia (10.5% O2) increased urine output and sodium and potassium excretion. Systemic arterial blood pressure fell during acute hypoxia. Levels of ANF significantly increased with acute hypoxia. The plasma levels of ANF during acute hypoxia were similar to those found following bolus doses of exogenous ANF which are known to cause diuresis, natriuresis and a fall in blood pressure. Increased ANF levels may play a role in mediating physiologic responses to hypoxia in the rat.