The effects of ventilation-to-perfusion (Va/Qc) maldistribution within the lungs on measured multiple gas rebreathing variables were studied in 14 dogs. The rebreathing method (using He, C18C, and C2H2) allows for measurements of pulmonary capillary blood flow (Qc), diffusing capacity (DLco), lung gas volume, and the combined pulmonary tissue and capillary blood volume (VTPC). Va/Qc imbalance was created by reversibly occluding the right main pulmonary artery or by reversibly obstructing the left main bronchus in eight dogs. Six additional dogs were ventilated with 10 cmH2O positive end-expiratory pressure (PEEP) to create a bimodal distribution of Va/Qc within the lungs. No significant alterations in computed rebreathing variables, except for a small (14%) decrease in DLco, occured during right main pulmonary artery occlusion, whereas obstruction of the left main bronchus caused parallel decreases (mean of 46%) in all rebreathing variables.