In renal failure, absolute calcium excretion is low, but fractional excretion (FE) of filtered load is increased. In order to determine the role of metabolic acidosis in contributing to increased FEca, we have studied thyropara-thyroidectomized dogs in a control phase and following the induction of chronic renal failure, both during spontaneous metabolic acidosis and after correction with NaHCO3. FEca was 3.7% in controls and increased to 13.7% in azotemic acidotic dogs (p < 0.01). After correction of acidosis FENa was not significantly changed, but FEca fell significantly, to 8.1% (p < 0.01), while glomerular filtration rate, plasma calcium and filtered calcium load were unchanged. Thus although FEca is increased in nonacidotic azotemic dogs, acidosis further enhances calcium excretion by inhibiting renal tubular calcium reabsorption. These effects of metabolic acidosis may contribute to hypocalcemia and bone disease in azotemia.