By quantitative immunoelectron microscopy using protein A-gold, the authors compared the content and distribution of immunoglobulin light chain (LC) antigens in glomeruli from 11 cases of renal amyloidosis with that in two cases of kappa LC glomerulopathy and two cases of diabetic glomerulosclerosis. In a supplementary study and using a similar immunogold technique, the authors identified amyloid A in deparaffinized renal tissue from three of the 11 cases of renal amyloidosis. Each patient had similar clinical manifestations (chronic renal failure with proteinuria) and similar glomerular morphology (thickened glomerular basement membranes and nodular expansion of the mesangium). In 12 cases (10 amyloid, 2 kappa LC), immunoelectron microscopy localized LC antigens over the glomerular deposits and allowed indirect tissue quantitation of each LC antigen to the various cellular and interstitial compartments. In 6 of the 11 cases of renal amyloidosis, the amyloid labeled only for lambda, and in one, only for kappa. In one patient with Waldenström's macroglobulinemia, who had a biclonal gammopathy, both LC were identified in the amyloid. In two cases, both of whom had a history of chronic suppurative lung disease, both LC antigens as well as amyloid A were localized to the amyloid fibrils. In only one case, in which glomerular amyloid labeled for amyloid A, the amyloid did not label for either LC. Whereas lambda LC-derived fibrils often appeared as spicules in the glomerular subepithelial space, other amyloid deposits usually accumulated in the subendothelial zone and did not form spicules. The epimembranous location of spicules suggested that the amyloid precursor protein transformed into amyloid fibrils after filtration into the urinary space. Presence of epimembranous spicules may explain the more severe proteinuric renal failure and the more rapid progression to glomerulosclerosis described in primary amyloidosis.