The effects of nonsteroidal anti-inflammatory drugs on renal function were studied in 15 chronically instrumented, unanesthetized beagles. In 9 dogs, bacterial peritonitis was induced by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. Six (control) dogs were subjected to laparotomy but were not implanted with an infected clot. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated using standard clearance methods. All measurements were performed after resuscitation with Ringer's lactate to a pulmonary capillary wedge pressure of 6 Torr. When measured 24 hr after laparotomy, there were no significant changes (relative to baseline) in GFR or ERPF in either the septic or control groups. In septic dogs, 60 min after the administration of either indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), GFR decreased an average of 26 +/- 11 ml/min (P = 0.043) and ERPF decreased an average of 100 +/- 27 ml/min (P = 0.02). In controls, administration of indomethacin (2 mg/kg) did not significantly affect either GFR or ERPF. These results suggest that renal function should be carefully monitored in clinical trials of nonsteroidal anti-inflammatory drugs in septic patients.