Lung inflation with positive airway pressure may have rapid and dynamic effects on myocardial contractile function. We designed this study to assess the magnitude and time to onset of myocardial function changes during the initiation of single positive pressure lung inflation at clinically relevant inflation pressures. In 8 anesthetized 40-kg pigs, left ventricular pressures and volumes were measured directly (conductance volumetry). A 15 cm H2O airway pressure plateau with lung inflation (PPLI-15) was performed, and 2 single beats from that sequence, one from resting apnea at zero airway pressure and the second from the point when the lungs were first maximally inflated, were selected for analysis. Systolic function variables for zero airway pressure and PPLI-15 were analyzed. Systolic elastance, derived from bilinear time-varying elastance curves, increased approximately 15% during PPLI-15 from zero airway pressure. This agreed with other systolic function variables that identified an increase in left ventricular contractile function for the lung inflation beat. Serial measurements of myocardial function should be conducted with constant airway pressure and lung inflation conditions.