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Positive direct immunofluorescence findings have been occasionally reported for human renal amyloidosis. However, no substantial information describing the frequency of immunomicroscopic pattern has been reported. Twenty-seven renal biopsy specimens with proven amyloidosis were studied by direct immunofluorescence using monospecific antisera against IgG, IgA, IgM, IgD, IgE, kappa and lambda light chains, C3, C4 properdin, alpha-2 macroglobulin, albumin, transferrin, and fibrinogen. Ten biopsy specimens were negative. The remaining specimens showed principally a diffuse immunofluorescent staining of the mesangial areas with various of the above fluorescein-labeled antisera except IgE, albumin, and transferrin antisera, which gave a consistently negative reaction. IgD, properdin, or fibrinogen were weakly identified in only one case. Immunoglobulins and C3 were observed in 14 cases. Kappa and/or lambda light chains were found in nine of ten biopsy specimens so tested. Positive immunofluorescent staining of other elements of the nephron was rarely observed. These results suggest that various immunoreactants, in addition to light chains, can be frequently detected in renal amyloidosis and that passive nonselective absorption of plasma proteins does not explain these immunomicroscopic findings.