To investigate if lysine acetylsalicylate influences the hemodynamic and diuretic responses to furosemide in cirrhosis, 21 nonazotemic patients with ascites were studied. In 8 patients (group 1), the renal plasma flow and glomerular filtration rate were serially measured before and during three 30-min periods after the i.v. administration of lysine acetylsalicylate (450 mg). In 7 patients (group 2), renal plasma flow, glomerular filtration rate, urine volume, and sodium excretion were measured before and during three 20-min periods after the i.v. administration of furosemide (40 mg). After a 45-min period in which urinary losses were restored, a similar study was performed before and after a second injection of furosemide (40 mg). Six patients (group 3) were studied with an identical protocol as group 2, except that the second injection of furosemide was preceded by the administration of lysine acetylsalicylate (450 mg). In 6 patients of group 1, lysine acetylsalicylate caused a marked and reversible reduction of renal plasma flow and glomerular filtration rate. In groups 2 and 3, the i.v. injections of furosemide alone produced a significant increase in renal plasma flow and glomerular filtration rate, and a marked diuresis and natriuresis. In patients of group 3, pretreatment with lysine acetylsalicylate suppressed the renal hemodynamic effect and markedly reduced the diuretic effect of the second injection of furosemide. Lysine acetylsalicylate did not cause the appearance of renal insufficiency in any of these patients. These results suggest that prostaglandins are involved in the renal response to furosemide in cirrhosis with ascites and that furosemide protects these patients from developing renal insufficiency after acute administration of nonsteroidal antiinflammatory agents.