Despite its acute inhibitory effect on bone formation in vitro, PTH has been shown to have an anabolic effect on bone in vivo and to stimulate cell proliferation in osteoblastic cell lines and organ cultures. We have examined the effects of PTH on cells derived from human trabecular bone and compared these effects with those on human skin fibroblasts. Human bone cells have the capacity to synthesize type I collagen and osteocalcin, and to respond to 1,25-dihydroxyvitamin D3 with an increase in the synthesis of osteocalcin and alkaline phosphatase. PTH stimulated adenylate cyclase activity at both low and high cell density. However, the same concentrations of hormone stimulated the proliferation of these cells only when they were cultured at a high cell density. The effect of PTH was bone cell specific in that no proliferative effect of PTH was detected in cultures of human skin fibroblasts obtained from the same donor and cultured under the same conditions. The effect of PTH on DNA synthesis by human bone cells may be important in the generation of a long term anabolic response to PTH.