Osteopetrosis in ia rats has been cured by combining whole-body irradiation with infusion of spleen cells from a normal littermate. The cure, first seen radiographically and histologically as areas of resorption below the epiphyseal plates of long bones, progressed to produce marrow cavities of normal proportions. Treatment of ia rats with either radiation or normal spleen cells alone was not successful. Furthermore, osteopetrosis was induced in normal littermates when radiation was combined with infusion of mutant (ia) spleen cells. These results show that spleen cells contribute to the resorbing capacity of the skeleton and suggest that osteoclasts might have a hematogenous origin.