Acetate metabolism in humans is not well known. Kinetic aspects of acetate were investigated in the postabsorptive state on healthy subjects. In a first study, six subjects were infused with a primed constant infusion of [1-13C]acetate for 3 h and a prime of NaH13CO3. No difference was found between arterialized and venous tracer enrichments from the arm, although arterialized acetate concentrations were higher (74 +/- 12 vs. 59 +/- 14 mumol/l, P < 0.05), suggesting that the hand muscles used but did not produce acetate in the postabsorptive state. Total body flux of acetate was 8.4 +/- 0.6 mumol.kg-1.min-1, of which 69 +/- 5% was oxidized. Acetate contributed to 6.5 +/- 0.4% of the basal energy expenditure. In a second study, five volunteers were submitted to a gastric infusion for 3 h followed by an intravenous infusion of [1-13C]acetate for 3 h. Higher fluxes were observed with the tracer gastric infusion, and the first-pass removal of acetate within the splanchnic bed was 60 +/- 7%. Acetate contributes significantly to the energy supply of the body. It is mainly used by the liver when produced in the gut.