We have demonstrated a transition in the expression of CD45 isoforms, from the expression of the high molecular weight CD45R to the low molecular weight CD45 p180 isoform on normal and on monoclonal (possibly malignant) B cells undergoing differentiation into plasma cells. The differentiation into plasma cells was shown by the loss of CD20 and CD21 surface antigens, a reduced expression, but in our system not a complete loss, of CD19, and the expression of the plasma cell marker PCA-1. We used three-color immunofluorescence to demonstrate the shift from CD45R to CD45 p180 on CD19+CD20-CD21- cells in cultures of normal cells stimulated by pokeweed mitogen (PWM). Furthermore, tissue sections of extramedullary plasmacytomas, where plasma cells were defined by morphology and expression of cytoplasmic Ig, showed a complete loss of CD45R and CD45 p180 antigens, although the cells retained expression of CD45 common determinants. Finally, we have analysed PBMC from patients with Waldenström's macroglobulinemia (WM) at various stages of disease, and demonstrated that the monoclonal B cell subset present in their peripheral blood is heterogeneous in the expression of CD45 isoforms, including cells bearing only CD45R, those with a transitional CD45R+CD45 p180+ phenotype, and those expressing only CD45 p180. Upon stimulation in vitro these cells show greatly increased expression of CD45 p180. The differential expression of CD45 isoforms within a clonal B cell subset in the blood of these patients suggests that the monoclonal B cells in WM represent a continuously differentiating lineage of CD45R+ mature B cells giving rise to CD45 p180+ pre-plasma cells.(ABSTRACT TRUNCATED AT 250 WORDS)