Background. Renal amyloidosis is associated with a variety of underlying disease processes. Although amyloid is identical in appearance in these diseases, the precursor proteins are different. Immunofluorescence microscopy has been used as the primary tool in the diagnostic evaluation of the underlying cause of renal AL-amyloidosis. The purpose of this study was to document the sensitivity of immunofluorescence microscopy in AL-amyloidosis. Methods. We reviewed 36 renal biopsies from patients with amyloidosis collected in two medical centres. All biopsies showed characteristic fibrillary deposits of amyloid on electron microscopy and stained positive with Congo red or Thioflavin-T. Results. Among these 36 patients, immunofluorescence staining for λ and κ light chains was negative or equivocal in 14 biopsies. Of these 14 patients, two patients had evidence of AA-amyloidosis. Twelve patients were found subsequently to have a plasma cell dyscrasia or multiple myeloma with monoclonal immunoglobulin and/or free light chains on immunofixation electrophoresis of urine or serum, and with evaluation of the bone marrow. Thus, 12 of 34 patients (35.3%) with proven AL-amyloidosis had negative immunofluorescence staining for κ and λ light chains. Conclusions. The data demonstrated the low sensitivity of immunofluorescence microscopy in the detection of AL-amyloidosis in the kidney and underscore the need to pursue additional diagnostic studies to identify this problem. © ERA-EDTA 2004; all rights reserved.