Whereas the liver is the major site of accumulation of 125I-labelled porcine calcitonin soon after injection in the rat, both human and salmon calcitonin were rapidly taken up in rat kidney, with relatively insignificant amounts found in the liver. In-vitro studies of degradation of 125I-labelled calcitonins showed that human calcitonin was readily degraded by most rat tissues but the major activity was found in a kidney microsomal fraction, whereas the liver supernatant was most active towards pig calcitonin. Salmon calcitonin was resistant to breakdown by all tissues and fractions except the kidney microsomal fraction, which rapidly degraded it to trichloroacetic acid-soluble fragments. Liver homogenates from a number of mammalian and non-mammalian species degraded pig calcitonin but had little effect on salmon calcitonin. The results show that the kidney is the most important organ in the metabolism of human and salmon calcitonin in the rat, while confirming that the liver is mainly responsible for the metabolism of porcine calcitonin.