Interleukin-1 (IL-1) is a potent stimulator of osteoclastic bone resorption in vitro and causes hypercalcemia and increased osteoclastic resorption when infused into normal mice for 72 h. However, its longer term or local effects on bone turnover in vivo are unknown. To study these, we injected ILla once daily for 3 days into the sc tissue over the calvariae of normal mice and examined its effects on calvarial bone morphology during the subsequent 4 weeks using quantitative histomorphometry. Increased bone resorption inside the calvariae and elevated plasma calcium concentrations were present 24 h after the last IL-1 injection. These early systemic effects were not prevented by indomethacin. During the following 3–4 weeks most of the bone on the injected side of the calvariae was resorbed by osteoclasts and was subsequently replaced by increased amounts of new bone. These longer term local effects on bone turnover were prevented by indomethacin. However, indomethacin did not prevent the formation of new bone inside the calvariae at sites of resorption induced by IL-1 independent of prostaglandin production. These findings indicate that IL-1 stimulates bone turnover systemically, independent of prostaglandin production, and that it has profound long term local effects on bone turnover that are mediated through prostaglandins.