We describe a monoclonal antibody (mAb), designated 1.C1, that causes rapid and vigorous aggregation among normal leucocytes and among T and myeloid/monocytic cell lines. As shown by competitive binding and sequential immunoprecipitation experiments, the antigen recognized by mAb 1.C1 is a 115,000 MW sialoglycoprotein, that corresponds to the human CD43 antigen, also known as leukosialin or sialophorin. The aggregation process starts within minutes and reaches maximum level 6-18 hr after addition of the antibody. It is dependent on active cell metabolism (inhibited at low temperatures and by a mixture of the metabolic poisons azide and 2-deoxy-D-glucose), a fluid plasma membrane (inhibited by pretreatment of the cells with paraformaldehyde) and an intact cytoskeleton (inhibited by cytochalasin B). Two reference CD43 antibodies (MEM-59 and DF-T1), both binding the same or closely related sialic acid-dependent epitope as mAb 1.C1, are also capable of inducing cell clump formation. CD11a/CD18 mAb block the 1.C1-induced adhesion of resting peripheral blood leucocytes, but not of haematopoietic cell line cells. In addition, mAb 1.C1 induces homotypic aggregation of K-562 cells, which do not express members of the beta 2 integrin subfamily on their surface. These data suggest that triggering of the CD43 antigen promotes homotypic cell adhesion that is mediated by both CD11a/CD18-dependent and -independent pathways.