The pathogenesis of chronic periodontitis involves the conversion of an established gingival lesion to an advanced periodontal lesion which most often is associated with extensive bone loss. Recently, both receptor and effector components of the host immune system have been implicated as causal factors in the process of bone resorption seen in various pathologic entities such as chronic periodontitis. The series of experiments proposed herein will explore the interaction and potential regulatory involvement of elements of the immune response with the process of bone resorption. We shall examine the role of cellular elements of the immune system (i.e., lymphocytes and mononuclear phagocytes) and immune effector molecules (e.g., lymphokines such as the osteoclast activating factor OAF) in bone resorption, as well as explore aspects of immune function and bone cell function in animal mutants (osteopetrotic mice) which lack normal bone resorption. We propose to conduct the following types of experiments; (1) transplantation of enriched populations of hematopoietic tissue cells between normal and osteopetrotic mice to study the origin of the cellular defect in bone resorption; (2) in vitro studies of immune function in lymphocytes and mononuclear phagocytes in osteopetrotic mice; (3) hormonal regulation of various functional parameters in mononuclear phagocytes related to bone resorption; (4) studies of lymphokine production in normal and osteopetrotic mice and its role in bone resorption; (5) mononuclear phagocyte chemotaxis and its relationship to bone resorption; (6) comparative studies of functional parameters in isolated bone cell populations of normal and osteopetrotic mice obtained by sequential enzymatic dissociation. The results of these investigations will provide significant information leading to a more complete understanding of the relationship of immune mechanisms to the process of bone resorption in chronic periodontitis as well as in normal skeletal remodeling.