Six chloralose-urethane anesthetized dogs (23 +/- 2 kg) underwent median thoracotomy (open pleural spaces) and constant mechanical ventilation with O-2. We conducted measurements at baseline and during 25 min of ventilation with 3.3 cmH(2)O positive end-expiratory pressure (PEEP3) or 10.7 cmH(2)O PEEP (PEEP11), including breath-by-breath values in the first 2 min after PEEP began. PEEP11 immediately decreased pulmonary CO2 elimination per breath (VCO2,br, digital integration and multiplication of exhaled flow and F-CO2) from 8.4 +/- 2.0 to 4.5 +/- 1.6 ml (P < 0.05) by significantly decreasing alveolar ventilation (V over dot A) (29% increase in anatomical dead space (VDana) and generation of high V over dot A/Q over dot regions) and by decreasing alveolar P-CO2 (PA(CO2)) from 42.5 +/- 3.5 to 35.9 +/- 3.5 Torr (decreased CO2 transfer to the lung as electromagnetic aortic cardiac output (Q over dot T) decreased by 51%). The immediate dilution of alveolar gas and PA(CO2) by fresh gas as PEEP increased functional residual capacity by 1152 +/- 216 ml was offset by simultaneous decreased expiratory volume and, hence, CO2 accumulation. Compared to baseline, the 17% reduction in V-CO2,V-br, was sustained at 25 min after addition of PEEP 11 because V over dot A remained depressed. Then, V-CO2,V-br could only be restored to baseline if PA(CO2) sufficiently increased. However, CO2 transport was still in unsteady state at 25 min of PEEP. Peripheral tissue retention of CO2 and the significant increase in mixed venous P-CO2 (P (v) over bar(CO2), 62.4 +/- 6.2 Torr) were not enough to normalize CO2 transfer to the lung and to sufficiently increase PA(CO2), especially during the continued depression in Q over dot T that occurred at higher PEEP. The sustained decrease in V-CO2,V-br during PEEP was not mirrored by changes in end-tidal P-CO2 (PET(CO2)).