When [125I]calcitonin was injected intravenously into rats the major site of accumulation of radioactivity was the liver, whereas [125I]parathyroid hormone was localized chiefly in the kidney. The distribution of [125I]bovine serum albumin and of Na [125I] was studied for comparison. Although most of the radioactivity of [125I]calcitonin was found in the soluble fractions of liver and kidney, significant binding to liver microsomes occurred. This fraction also bound an appreciable amount of the radioactivity of [125I]parathyroid hormone. The uptake of [125I]calcitonin by liver could be inhibited by the simultaneous injection of unlabelled calcitonin, but not by that of parathyroid hormone, insulin or adrenocorticotrophic hormone. These results indicate a role for the liver and kidney in the early clearance of calcitonin and parathyroid hormone respectively. It is likely that the liver is the major site of the metabolism of calcitonin in vivo.