We evaluated the effect of indomethacin on renal function in a sodium-restricted state in control subjects and in patients with systemic lupus erythematosus (SLE) without major disease activity and with normal or only slightly impaired glomerular filtration rate (GFR). In the patients with SLE indomethacin 150 mg daily induced a fall in GFR of mean 15.8%, while effective renal plasma flow remained constant. Neither effective renal plasma flow, nor GFR changed significantly in the controls. One should be aware that nonsteroidal anti-inflammatory drugs (NSAID) may decrease GFR in SLE, also in patients without disease activity and with normal or only slightly impaired GFR. As effective renal plasma flow remained constant, it is suggested that the indomethacin-induced fall in GFR in SLE is caused by mesangial contraction.