It is shown that thrombin (0.1–7 units/ml) stimulates calcium mobilization and bone matrix degradation, as indicated by release of [3H]proline, from cultured calvarial bones. The second finding in this paper, that indomethacin blocks the stimulating effect of thrombin on bone resorption, is consistent with the concept that prostaglandin synthesis may be involved in this process. It is suggested that thrombin is a potential mediator of bone resorption associated with inflammatory and malignant processes.