The purpose of this study was to evaluate transthoracic impedance (Z) as an index of total lung liquid content at constant lung gas volume (LGV). To this end we produced rapid changes in pulmonary blood volume (PBV) in anesthetized, paralyzed, closed-chest dogs with the airway occluded at functional residual capacity. Changes in PBV produced by inflation of balloons on catheters positioned in the left atrium (LA) or inferior vena cava (IVC) were estimated from the changes in chest wall recoil pressure, using the chest wall as a plethysmograph after calibration with changes in LGV. Whereas Z increased linearly with decreases in PBV (1-6 ml/kg) produced by the IVC balloon (% delta Z/delta PBV = -0.43 ml/kg, r = -0.81), Z did not change significantly with increases in PBV (1-6 ml/kg) produced by the LA balloon. These observations indicate that changes in PBV are not the primary determinant of changes in Z and raise the possibility that other hemodynamic events are more important. Whereas aortic pressure decreased with both IVC and LA balloon inflations, right atrial pressure (Pra) increased with mitral valve obstruction and decreased with IVC obstruction. Changes in chest wall blood volume in response to changes in Pra could explain the changes in thoracic impedance. Thus, even at constant LGV, events in the systemic circulation appear to invalidate Z as an indicator of lung liquid content.