Evidence for amyloid fibril formation in rough endoplasmic reticulum (RER) of plasma cells from the duodenum of a 62-year-old man with localized A lambda amyloidosis is described. The inclusions in RER of plasma cells were composed of tightly packed, regular arrays of fibrils cut in both longitudinal and cross-sections. The fibrils within the inclusions, measuring 10 nm in width, were oriented parallel to the long axis of the inclusions. By immunoelectron microscopy with an antihuman A lambda antiserum, gold particles labeled the fibrils located both in the RER of plasma cells and in the extracellular space. In addition, electron-dense material in the dilated RER was occasionally labeled. These findings suggest that at least some amyloid fibrils are unequivocally created in the RER of plasma cells.