1. The metabolic clearance rate (MCR) of human calcitonin was measured in 12 normal subjects and four patients with Paget's disease by the infusion of synthetic human calcitonin (15–40 μg/h for 2–24 h), and in 10 additional patients with Paget's disease from the disappearance rate of immunoreactive calcitonin from plasma after the intravenous injection of large doses of synthetic human calcitonin (0·5–1·0 mg).
2. The estimated MCR during the infusion studies (range 531–1224 litres/day) was similar to that calculated from the disappearance of large doses of synthetic human calcitonin injected intravenously in patients with Paget's disease (mean = 1035 litres/day; range = 593–1408 litres/day).
3. An eightfold range in the basal values of plasma immunoreactive calcitonin, in spite of the presence of a relatively constant MCR, suggests that the variation in basal plasma calcitonin was due principally to variation in the endogenous secretion rate for calcitonin.
4. The results suggest that the endogenous secretion rate for calcitonin is low in normal subjects (mean 124 ± sem 24 μg/day), and give a basis for selecting the doses of calcitonin which can be considered physiological.