Two patients with systemic lupus erythematosus and mild renal functional impairment were treated with ibuprofen, one of the phenylproprionic nonsteroidal anti-inflammatory drugs. Within days after the onset of therapy, both developed renal insufficiency manifested by elevated serum creatinine levels, increased proteinuria and active urinary sediments; 1 patient was oliguric. Renal biopsies disclosed mesangial proliferative lupus glomerulonephritis and acute tubular necrosis, the latter more pronounced in the oliguric patient. Renal failure resolved following discontinuation of ibuprofen and supportive therapy. Apparently, altered blood flow, mediated through the well-known prostaglandin synthetase inhibitory effects of ibuprofen, resulted in tubular necrosis. This undesirable complication of ibuprofen therapy may be enhanced in patients with underlying renal disease, and may be a factor governing the limitation of its usage.