As the initial step in examining the metabolic basis for acetate intolerance, we have tested the hypothesis that excessive adenosine triphosphate (ATP) degradation occurs during hemodialysis against acetate dialysate (compared with the degree of degradation occurring during dialysis against bicarbonate dialysate). Seven patients undergoing long-term dialysis were infused with carbon 14--labeled 8-adenine, and their response to dialysis against acetate was compared with their response to dialysis against bicarbonate. The following changes were observed. During dialysis against acetate, the mean dialysate uric acid--to-creatinine ratio levels were significantly higher than the mean levels observed after dialysis against bicarbonate (p less than 0.001). The mean dialysate uric acid radioactivity--to-creatinine ratio and inosine, hypoxanthine, and xanthine radioactivity--to-creatinine ratio levels were significantly increased during dialysis against acetate (p less than 0.001). There was no significant change in plasma venous hypoxanthine level, but during dialysis against acetate, the arterial hypoxanthine levels (3.7 +/- 1.6 mumol/L) at 60 minutes were significantly higher than the levels observed after dialysis against bicarbonate (1.4 +/- 0.5 mumol/L) (p less than 0.01). These data provide evidence that excessive ATP degradation occurs during hemodialysis against acetate but not during hemodialysis against bicarbonate dialysate.