This study examines endogenous acid production in a group of stable chronic hemodialysis patients with no residual renal function who were admitted to the chronic hemodialysis unit of Mount Sinai Hospital. Net acid production was estimated by the change in body bicarbonate content, which occurs in the interdialytic period. The body bicarbonate content at any time was measured by multiplying the concentration of blood bicarbonate by the apparent bicarbonate space at that time. The apparent bicarbonate space was determined by the change in blood bicarbonate concentration induced by the intravenous administration of a known amount of sodium bicarbonate. Daily sulfuric acid production was also estimated from the reduction in body sulfate content during dialysis. The interdialytic net acid production was measured at approximately 28 mEq/d, a value much lower than that predicted from the protein catabolic rate. This reduced acid production can be explained by reduced sulfuric acid and organic acid production. The mechanism of reduced sulfuric acid production is unknown. Reduced organic acid production is explained partly by the absence of renal excretion of metabolizable organic anions, leaving only the nonmetabolizable fraction as the main source of acid in the interdialytic period.