The purpose of this study was to clarify the means by which lithium induced a greatly diminished phosphaturic response to parathyroid hormone (PTH). Acutely thyroparathyroidectomized lithium-treated rats did not respond to PTH whereas similarly prepared animals in the presence of metabolic or respiratory acidosis exhibited a large phosphaturic response. Respiratory alkalosis significantly decreased fractional phosphate excretion and blocked the phosphaturic effect of PTH whereas PTH induced increases in cyclic AMP excretion in these animals. Lithium increased urinary excretion of oxoglutarate and citrate. In metabolic acidosis the restoration of PTH-dependent phosphaturia is accompanied by decreased organic acid excretion. No significant decrease of urinary citrate and oxoglutarate excretion occurred in respiratory acidosis in lithium-treated rats. It is suggested that PTH-dependent phosphate transport is mediated by intracellular pH but the increased excretion of citrate and oxoglutarate may reflect high intracellular levels of bicarbonate.