The purpose of the study was to investigate the possible involvement of prostaglandins (PG) and thromboxanes (TX) in the cardiovascular and pulmonary changes associated with the use of continuous positive-pressure ventilation (CPPV). Indomethacin (IND), an inhibitor of PG cyclo-oxygenase, was used to block the synthesis and release of PG and TX in the lung after alveolar stretch with CPPV. Groups of dogs received CPPV (buffer group) or CPPV + IND 5 mg/kh iv (CPPV + IND). Pulmonary edema or alveolar hemorrhage was evident in 5 of 6 buffer animals. This damage was also manifested by a 50% decrease in lung compliance. However, IND appeared to block development of lung tissue damage in 5 of 6 CPPV + IND dogs and compliance remained normal. A 52% lowering of cardiac index (CI) in the buffer group paralleled a 71% reduction of left ventricular dP/dt max (first derivative of left ventricular pressure). Peak transmural right heart filling pressure decreased only 15%. in contrast, the 38% decrement of CI in the CPPV + IND animals was coupled with a 98% reduction in filling pressure, but only a 25% decrease in dP/dt max. CPPV-induced changes may have been related, in part, to the release of cytotoxic negative inotrope(s) from damaged alveolar membranes because IND pretreatment blocked this damage.