We investigated the effect of airway closure and alveolar collapse on the large-volume deflation and inflation transpulmonary pressure-volume (Ptp-V) curves of five postmortem excised human lungs. For stepwise static cycles, no inflection occurred on the deflation curve, while either one or two inflections occurred on the inflation curve. These relations were stimulated by a multicompartment model, which assumed a bimodal distribution of compartmental collapse-pressure differences. The simulations indicate that alveolar collapse can occur without causing an inflection on the deflation curve and that hysteresis in reopening of collapsed alveoli on inflation can account for a major portion of Ptp-V hysteresis. In contrast, for slow dynamic cycles, an inflection occurred on the experimental deflation Ptp-V curve, and when inflations were begun at sufficiently low volumes, volume did not change until a threshold pressure difference was reached about which PtP began to oscillate as lung volume increased. These differences in the stepwise static and dynamic Ptp-V curves can result from sustained airway closure on deflation and popping-opening on inflation.