As little as 3-5 cm H2O increase in proximal airway pressure applied to normal lung reduces cardiac output. It is postulated that decreased pulmonary compliance in respiratory distress syndrome (RDS) acts as a barrier thus offsetting this effect. Since cardiac output is not routinely measured, severe reduction in it could accompany regression of disease while maintaining the same airway pressure. This study was undertaken to determine whether tissue oxygen available (O2a) could be used to detect changes in perfusion during continuous positive pressure breating (CPPB). CPPB was evaluated in 10 normal rabbits (CL = 9.5 +/- 1.8 cc/g at 25 cm H2O) and in 10 pulmonary-damaged rabbits (CL = 5.5 +/- 1.4 cc/g at 25 cm H2O) produced by subjecting them to 100% O2. Airway pressure was increased from 0-15 cm H2O in 3 cm H2O increments at 10-min intervals. O2a and PaO2 were monitored continuously. In the normal group, O2a decreased at 3 cm H2O airway pressure, reaching 22% of control at 12 cm H2O, at which pressure PaO2 decreased. Breathing 100% O2 at this airway pressure increased PaO2 to 408 mm Hg, whereas O2a returned to 45% of control. In the experimental group, O2a decreased at 9 cm H2O airway pressure, at 12 cm H2O it was 36% of control at which pressure PaO2 decreased slightly. Breathing 100% O2 at this airway pressure increased PaO2 to 316 mm Hg, and increased O2a to 200% of control. These data indicate that with excessive airway pressure, muscle hypoxia may exist during systemic hyperoxemia and that a low compliance lung exerts a protective effect on O2a. Since changes in cardiac output during CPPB are compliance dependent, and since O2a is perfusion dependent, tissue oxygen available could provide a means of selecting optimal airway pressure during CPPB.