Animal models of osteopetrosis have led us to consider this condition to be an immune disease. In both the hereditary from in the op/op mutant rat and in experimentally induced from by Cl2MDP, osteopetrosis is associated with immune deficiencies, such as the inhibition of the mitogenic response of T lymphocytes, the inability to develop adjuvant arthritis. In particular, the differentiation of the thymus dependent macrophages is inhibited in the mouse treated with Cl2MDP. These animal models illustrate the relationships between the immune system and the bone regeneration system. They enable the study of the relationship between T lymphocytes, macrophages and osteoclasts.