The incidence of proteinuria in D-penicillamine-treated rheumatoid arthritis has been between 10% and 20% in the 1st year of therapy; afterward, few develop proteinuria. Incidence is related to both quantity of penicillamine administered and inherent response variability. About 1/3 of those with proteinuria may proceed to a nephrotic syndrome if therapy is continued. Light microscopy of renal biopsy tissue shows only minimal glomerular changes. Electron microscopy reveals sub-epithelial electron-dense deposits and fusion of epithelial cell processes. Immunofluorescence microscopy demonstrates granular capillary wall deposits of IgG and C3.