Arterial hypoxemia in acute experimental pneumococcal pneumonia is caused primarily by persistence of pulmonary blood flow to lung regions consolidated by pneumonia, which results in an intrapulmonary shunt. In order to test the hypothesis that in acute pneumonia indomethacin or acetylsalicylic acid (ASA) would improve gas exchange, as has been observed in some other disease models, 15 pentobarbital-anesthetized dogs with acute lobar pneumonia caused by Streptococcus pneumoniae type 3 were studied. After baseline measurements of pulmonary gas exchange, central hemodynamics and radionuclide-labeled microsphere determination of regional distribution of pulmonary blood flow, the dogs were randomly assigned to receive an intravenous infusion of indomethacin (2 mg/kg, n = 5), ASA, (100 mg/kg, n = 5) or a saline infusion (control, n = 5). All measurements were then repeated 30 and 60 min after infusion. Although there were no significant changes in the control group, PaO2 during O2 ventilation increased from a mean +/- SD value of 104 +/- 46 mmHg at baseline to 180 +/- 73 mmHg after ASA and from 262 +/- 173 to 361 +/- 134 mmHg after indomethacin. These improvements in PaO2 were associated with a decrease in shunt from 0.38 +/- 0.12 to 0.23 +/- 0.03 with ASA and from 0.29 +/- 0.21 to 0.21 +/- 0.08 with indomethacin. The reduction in shunt in both treatment groups was attributable to a fall in the fraction of the pulmonary blood flow perfusing the consolidated lung regions, from 33 +/- 8 to 21 +/- 5% after ASA and from 33 +/- 12 to 22 +/- 9% after indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)