A study was conducted to investigate the influence of systemic inflammation on heterotopic bone formation induced by bone morphogenetic protein (BMP). Five-milligram pellets of BMP were implanted in mice with type II collagen-induced arthritis. Intraperitoneal injections of interleukin-1 (IL-1) were also administered to a group of mice without collagen-induced arthritis. The amount of BMP-induced heterotopic bone formation was evaluated by soft X-ray radiography, histology, and assay of calcium content. BMP-induced heterotopic bone formation was markedly enhanced in mice with collagen-induced arthritis, and also in IL-1-treated mice. These findings suggest that bone formation is enhanced in mice with collagen-induced arthritis, and that IL-1 may be responsible.