Respiratory alkalosis induced hypophosphatemia and hypophosphaturia in intact animals. The present studies evaluated the effect of respiratory alkalosis on tissue phosphate distribution and renal phosphate transport in the presence and absence of parathyroid hormone (PTH). Respiratory alkalosis decreased plasma phosphate concentration and increased phosphate concentrations in muscle and liver. It decreased fractional phosphate excretion (FEPi) from 6.1 +/- 1.4 to 0.6 +/- 0.2%. In thyroparathyroidectomized (TPTX) rats infused with 20 mM phosphate, respiratory alkalosis decreased FEPi from 15.0 +/- 0.9 to 5.5 +/- 0.1%. PTH or dibutyryl cAMP administration produced a phosphaturia that was blunted by respiratory alkalosis. The phosphaturic response to PTH was also blunted in hypocapnic rats in which alkalosis was prevented by infusion of HCl. We conclude that respiratory alkalosis increases phosphate uptake by muscle, which largely accounts for the hypophosphatemia. The kidney response with increased phosphate reabsorption independent of plasma and kidney phosphate concentrations and with refractoriness to the phosphaturic effect of PTH. This refractoriness to the phosphaturic effect of PTH is due to decreased PCO2 rather than to the concomitant extracellular alkalosis.