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Sodium acetate was infused intravenously at 2.5 mmoles/min for 60 min into 6 normal subjects and 6 non-insulin dependent diabetic patients. In control experiments the same subjects received equimolar sodium bicarbonate infusions. Plasma non-esterified fatty acid and blood glycerol levels fell during acetate infusion in both groups, suggesting impairment of lipolysis. The respiratory quotient fell on acetate infusion as expected, although total energy expenditure was unaffected. If acetate oxidation was assumed to be 90 per cent of the infusion rate, then it accounted for about 40 per cent of total oxygen consumption; fat oxidation was reduced, whilst carbohydrate oxidation was unchanged. These results suggest that resting energy expenditure is maintained during acetate infusion since acetate replaces fat as an oxidative fuel, without affecting glucose oxidation. The reduction in fat oxidation appears to be due to reduced fat mobilization from adipose tissue. The metabolic effects of acetate infusion are similar in normal and in non-insulin dependent diabetic subjects.