The relation between serum calcium and the extent of metastatic bone disease as judged by radionuclide bone scan was examined in a consecutive series of 195 patients with malignant disease. Of 87 patients with hypercalcaemia, 40% had no evidence of skeletal metastatic bone disease and serum calcium values. Of 160 patients judged to have bone-scan evidence of metastatic skeletal involvement, only 32.5% were significantly hypercalcaemic. Further, a negative correlation was found between the extent of metastatic bone disease and serum calcium value. The development of hypercalcaemia in malignancy is not directly related to the presence or extent of metastatic bone disease. It is suggested that the development of hypercalcaemia may depend on an alternative mechanism, such as the production of a humoral substance by tumour tissue, having its effect on calcium metabolism at sites or organs distant from local areas of tumor involvement.