We studied the urinary excretion of immunoreactive prostaglandin E-like material (iPGE) and renal function in 7 women with systemic lupus erythematosus to evaluate the relation between urinary iPGE and the increase in serum creatinine in patients taking aspirin. The mean pretreatment excretion of urinary iPGE in patients with lupus erythematosus, 42.7 ± 6.4 ng/h, was significantly higher than the value of 29.0 ± 1.9 ng/h for normal subjects (P<0.02). With aspirin, the urinary iPGE decreased an average of 45% (P<0.001). Increases in serum creatinine and blood urea nitrogen confirmed our previous clinical observations. The concomitant mean fall in creatinine clearance of 18% (P±0.001) was accompanied by a 14% decrease in inulin clearance (P<0.005); p-aminohippurate clearance fell 29% (P<0.005). The decline in urinary iPGE preceded the fall in creatinine clearance but was significantly correlated with it (r = 0.78; P<0.001). The observed changes reversed rapidly when aspirin was stopped. These data show that, in these patients with high urinary iPGE excretion, aspirin causes significant changes in renal function that may be mediated by the inhibition of prostaglandin synthesis.