The hypothesis that parathyroid hormone and carbonic anhydrase inhibitors have a common mechanism or site of action on phosphate reabsorption by the renal tubule was tested by administration of parathyroid hormone in the absence and presence of acetazolamide in thyroparathyroidectomized dogs. Re-collection micropuncture and electron probe microanalysis methodologies were utilized. In the absence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (and volume) from the proximal tubule from 25 +/- 2 to 38 +/- 3%, P less than 0.025, and increased fractional phosphate excretion from 3.8 +/- 1.2 to 19.9 +/- 3.7%, P less than 0.005 (eight dogs). In the presence of acetazolamide, parathyroid hormone increased fractional delivery of phosphate (but not volume) from the proximal tubule from 50 +/- 4 to 58 +/- 5%, P less than 0.025, and increased fractional excretion of phosphate from 8.7 +/- 2.2 to 31.0 +/- 4.3%, P less than 0.001 (12 dogs). Thus, the effects of parathyroid hormone were additive to the effects of maximal inhibition of carbonic anhydrase indicating that parathyroid hormone and carbonic anhydrase inhibitors have different mechanisms of action on phosphate reabsorption by the renal tubule. In addition, phosphate reabsorption beyond the point of micropuncture in the late proximal tubule was much more markedly inhibited by parathyroid hormone than by acetazolamide.