Concern has been expressed that the acetate (Ac) used in dialysate may stimulate lipid synthesis and accelerate atherosclerosis. Tolchin, et al(10) calculated the fractional generation of bicarbonate from Ac, in order to estimate the amount of Ac entering the citric acid cycle. However, these calculations were based upon the assumption that the bicarbonate space was 60% of body weight. These investigators estimated that 91-93% of Ac was metabolized to bicarbonate; they suggested that 7-9% Ac may have been used for lipid synthesis. In the present experiments, 6 hemodialysis patients were infused with 2 mmoles Na bicarbonate/kg to measure directly the bicarbonate space for each patient. The bicarbonate space was 44 +/- 2% of body weight. On a separate day, the same patients were infused with 2 mmoles Na Ac/kg. Using the measured bicarbonate space, the calculated fractional generation of bicarbonate from Ac was 98 +/- 4%. Rabbit experiments were also performed with an atherogenic diet, supplemented with 10% Ac, 10% bicarbonate, or 10% glucose. After 8 mos of dietary treatment, there was no difference in serum triglycerides, cholesterol, or extent of atherosclerosis between groups. The human and animal experiments both provide evidence that Ac in dialysate does not stimulate lipid synthesis.