The study of the elimination kinetics of peptide hormones in humans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1-84) after adenoma removal in primary hyperparathyroidism, based on a 2-compartment model. In 12 patients, blood samples were drawn in short intervals preoperatively, during surgery, and up to 4 days postoperatively. Plasma levels of PTH (1-84), calcium (Ca), and inorganic phosphate were determined. PTH (1-84) levels remained constant before surgery and during adenoma preparation; 2.5 min after clamping of the adenoma's blood supply, PTH (1-84) decreased (34.9 +/- 4.8 vs. 23.3 +/- 2.9 pmol/L, mean +/- SEM, P < 0.001) and then reached a minimum of 0.96 +/- 0.06 pmol/L at 5 h. The elimination half-lives for PTH (1-84) were 3.43 +/- 0.1 min and 81.7 +/- 12.7 min. Ionized Ca started to decrease 30 min after adenoma removal (1.58 +/- 0.04 vs. 1.56 +/- 0.04 pmol/L, P < 0.001). This decrease was paralleled by a decrease in total Ca. Inorganic phosphate increased 24 h after adenoma removal. In conclusion, PTH (1-84) elimination after adenectomy is characterized by a rapid initial decrease and a subsequent prolonged period with a lower elimination rate. This elimination pattern may also apply to other human peptide hormones.