This study explores the use of immunofluorescence on routine formalin-fixed paraffin-embedded tissue to distinguish monoclonal from polyclonal lymphoplasmacytic proliferations. Sixteen tissues containing plasma cell or lymphocyte and plasma cell proliferations were studied. Five-micron sections were deparaffinized in xylene, rehydrated, and treated with 0.1% trypsin for two hours. After washing with phosphate-buffered saline, separate sections were stained with fluorescein-conjugated antibody to IgG, IgA, IgM, IgD, and IgE, and a single section was stained with both fluorescein-conjugated anti-kappa and rhodamine-conjugated antilambda. The latter section was useful to distinguish nonspecific adsorption of the fluorochromes. Where possible, results were correlated with immunoelectrophoretic studies of serum and urine. Eleven specimens with monoclonal and four specimens with polyclonal lymphoplasmacytic proliferations were readily identified, including a case of giant lymph node hyperplasia with a monoclonal IgDK plasma cell component (confirmed by specific absorption studies). Identification of monoclonality by immunofluorescence preceded immunoelectrophoretic identification in one case. One other case gave equivocal results by fluorescence. Further, the method worked on formalin-fixed decalcified tissues, although a somewhat heavier background staining was noted. This method offers a simple, reliable technique to establish or confirm the diagnosis of monoclonal lymphoplasmacytic lesions.