Small but statistically significant negative calcium balances were found in each of eight studies in seven patients with chronic azotemic renal disease when stable metabolic acidosis was present. Only small quantities of calcium were excreted in the urine, but fecal calcium excretion equaled or exceeded dietary intake. Complete and continuous correction of acidosis by NaHCO(3) therapy reduced both urinary and fecal calcium excretion and produced a daily calcium balance indistinguishable from zero. Apparent acid retention was found throughout the studies during acidosis, despite no further reduction of the serum bicarbonate concentration. The negative calcium balances that accompanied acid retention support the suggestion that slow titration of alkaline bone salts provides an additional buffer reservoir in chronic metabolic acidosis. The treatment of metabolic acidosis prevented further calcium losses but did not induce net calcium retention. It is suggested that the normal homeostatic responses of the body to the alterations in ionized calcium and calcium distribution produced by raising the serum bicarbonate might paradoxically retard the repair of skeletal calcium deficits.