The disappearance of plasma PTH after parathyroidectomy was assessed in patients with primary hyperparathyroidism and normal renal function, chronic renal failure or restored renal function (after transplantation). Plasma PTH levels were determined by renal cytochemical bioassay and by midregion and carboxyl-terminal RIAs. Baseline PTH levels were lower in each patient when assessed by bioassay than when determined by RIA, and the rate of hormone disappearance was faster when determined by bioassay than when measured by RIA. This difference was accentuated in chronic renal failure due to prolongation of the disappearance rates of midregion and carboxyl-terminal immunoreactivity. The half-life of bioassayable hormone in patients with chronic renal failure was prolonged less than 2-fold compared to the half-life in patients with normal or restored renal function. The results emphasize the discordance between levels of bioactive and immunoreactive hormone regardless of renal function, demonstrate that this discordance is augmented after acute reduction in circulating hormone, and show that it is further increased when kidney function is impaired. The studies also implicate extrarenal mechanisms as a major factor in the clearance of bioactive hormone in established renal failure.