Lymphocyte function-associated antigen-1 (LFA-1) (CD11a/CD18) expression on bone marrow-derived plasma cells from normal individuals, patients with monoclonal gammopathies of undetermined significance (MGUS), and patients with multiple myeloma (MM) was studied by immunofluorescence microscopy and flow cytometry using a new monoclonal antibody (MoAb) F8.8. This MoAb recognizes the alpha-chain (CD11a) of LFA-1 as determined by immunoprecipitation, and inhibits T-cell-induced cytotoxicity. Although the F8.8 MoAb stains unstimulated peripheral blood T cells with the same mean fluorescence intensity as other anti-CD11a MoAbs, it proved to be superior in detecting CD11a on plasma cells as compared with reference MoAbs. Using the anti-CD11a MoAb F8.8, a strong correlation was found between LFA-1 expression and disease activity in MM, as defined by clinical performance and serum M-protein level. Hardly any LFA-1+ plasma cells were detected in normal individuals, patients with MGUS, and MM patients in a nonactive phase of their disease, while plasma cells of some MM patients with active disease and all patients with fulminant disease expressed LFA-1. Plasma cell LFA-1 expression correlated well with the labeling index (LI) of the tumors in the individual patients. The relation between LFA-1 expression and the tumor growth suggests an involvement of this adhesion molecule in cellular interactions resulting in plasma cell proliferation.