We have examined the effects of an acidic fibroblast growth factor (aFGF) on bone cell growth and differentiation and on osteoclastic resorption using rat fetus organ cultured calvariae and long bones, respectively. Low concentrations of this aFGF stimulated DNA synthesis (1.28 ng/ml) and inhibited collagen formation (1.28 ng/ml) and alkaline phosphatase activity (0.64 ng/ml) in the isolated calvariae. The inhibition of collagen synthesis was independent of the aFGF's mitogenic effect, and was evident in periosteum-containing and periosteum-free bones, pointing to osteoblasts as the aFGF-responsive cells. Our preparation of aFGF enhanced resorption in the long bones by a calcitonin-inhibitable mechanism. PGE2 release accompanied and indomethacin prevented the enhancement of resorption. By contrast, indomethacin did not block the stimulation of DNA and collagen synthesis caused by our aFGF. These results indicate that our aFGF exerts a PGE2-independent effect on DNA synthesis and collagen synthesis and a PGE2-dependent effect on resorption in bone tissue in vitro.