The management of critically ill patients requires a fundamental understanding of cardiopulmonary interactions associated with mechanical ventilation. The hemodynamic changes due to ventilation are a result of changes in lung volume and intrathoracic pressure (ITP) and can occur during spontaneous or positive pressure ventilation despite constant tidal volumes. Pulmonary vascular resistance (PVR) and mechanical heart-lung interactions play prominent roles in determining the hemodynamic response to mechanical ventilation. Lung inflation alters PVR and right ventricular wall tension and, at high lung volume, mechanically limits cardiac volumes. The authors will consider the mechanisms of the effects of ITP on the pulmonary arterial and venous branches. These effects will aid in understanding the complex interactions between ventilation and right and left ventricular pressures and volumes, as well as the influence of lung inflation pressure on ventricular interdependence.