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To evaluate the effects of an acute glucose load on circulating atrial natriuretic factor (ANF) levels.We investigated plasma ANF, glucose and insulin levels before and after intravenous administration of 50% D-glucose (300 mg/kg body weight) in healthy, normal volunteers.In study group A (n = 30) plasma ANF was found to be increased significantly 30min after the glucose load. In study group B (n = 55) the response of plasma ANF over time was assessed. A peak plasma ANF response was observed 10min after intravenous glucose loading; thereafter, plasma ANF levels returned gradually to basal levels at 50min after glucose injection. The latter produced in both study groups a similar acute hyperglycaemia, and in group B the expected concomitant hyperinsulinaemia.These observations demonstrate that, in normal humans, acute marked hyperglycaemia is accompanied by a rapid increase in circulating ANF levels. In this metabolic interaction, ANF might counteract the renal sodium-retaining effect of acute hyperglycaemia and hyperinsulinaemia.