Leukocyte/endothelial cell adhesion molecules are essential mediators of both immune and inflammatory responses. However, their specific roles in the initiation and progression of inflammatory diseases remain largely undefined. The focus of our laboratory is the identification of the adhesion molecule interactions that mediate leukocyte recruitment and tissue damage during the development of rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. For these studies, we use a basic genetic approach in mice, analyzing different gene-targeted adhesion molecule mutants, or "knockouts," in murine disease models. Our findings suggest that loss of intercellular adhesion molecule-1 significantly inhibits the development of arthritis and glomerulonephritis, while selectin deficiency results in accelerated development of joint and kidney inflammation. Our results also indicate that the β2 integrins may play a key role in regulating the initiation of psoriasiform skin diseases.