Nitric oxide is a gas radical regulating cell, behaviour in the cardiovascular, immune, and central nervous systems. It has now been established as an important signalling molecule in bone, However, the effects of this gas radical on osteoblastic function are still unclear; in fact, while NO seems to be involved in anabolic processes mediated by mechanical strain, sex hormones and fracture healing, it also mediates catabolic processes in response to inflammation. We show here that a slow and moderate release of nitric oxide stimulates the replication of primary rat osteoblasts and alkaline phosphatase activity, while a rapid release and high concentrations of NO inhibit proliferation and induce apoptosis. We demonstrate that both the stimulatory and apoptosis-inducing effects of NO on primary osteoblasts are mediated by the second messenger cGMP, since both are abolished by the guanylate cyclase inhibitor ODQ.