We report here that MAb to human LFA-1 inhibit spontaneous homotypic adhesions of human B lymphocytes. This is, to our knowledge, the first report of a MAb that inhibits human homotypic intercellular adhesions for any cell type. LFA-1 has previously been recognized as a molecule capable of regulating specific immunologic adhesions between T lymphocytes and antigen-bearing target cells. The present findings show that the role of LFA-1 is not limited to adhesions initiated by specific immunologic recognition. The results indicate that the LFA-1 molecule is capable of regulating lymphocyte adhesions, possibly because it is a direct participant in adhesion formation.