Oleic acid causes permeability pulmonary edema in the lung, resulting in impairment of gas-exchange and ventilation-perfusion heterogeneity and mismatch. Previous studies have shown that by using the multiple-breath helium washout (MBHW) technique, ventilation inhomogeneity (VI) can be quantitatively partitioned into two components, i.e., convective-dependent inhomogeneity (cdi) and diffusive-convective-dependent inhomogeneity (dcdi). Changes in VI, as represented by the normalized slope of the phase III alveolar plateau, were studied for 120 min in five anesthetized mongrel dogs that were ventilated under paralysis by a constant-flow linear motor ventilator. These animals received oleic acid (0.1 mg/kg) infusion into the right atrium at t = 0. MBHWs were done in duplicate for 18 breaths every 40 min afterward. Three other dogs that received only normal saline served as controls. The data show that, after oleic acid infusion, dcdi, which represents VI in peripheral airways, is responsible for the increasing total VI as lung water accumulates progressively over time. The cdi, which represents VI between larger conductive airways, remains relatively constant throughout. This observation can be explained by increases in the heterogeneity of tissue compliance in the periphery, distal airway closure, or by decreases in ventilation through collateral channels.