Alveolar gas concentrations were simulated in an asymmetrically branching model of a human lung acinus based on morphometric measurements. The structure was expansile so that convective flow into and out of every part was proportional to its volume. Despite the homogeneous volume change solution of a differential equation for simultaneous convection and molecular diffusion following a 1-liter breath of O2 at 0.5 l/s predicted substantial inhomogeneity of O2 concentrations. This was reflected in a twofold range of inspired gas per unit volume computed from O2 concentrations averaged throughout expiration. Even a 10-s breath hold at end inspiration did not result in uniform concentrations. Larger breaths, corresponding to a ventilation of 60 l/min, increased the degree of inhomogeneity 50%. Diffusive pendelluft at intra-acinar branch points during expiration produced a sloping alveolar plateau of 0.53% N2/l, i.e., much smaller than that measured from the whole lung in vivo. Similarly, an estimate of single-breath mixing efficiency also indicated a much smaller degree of inhomogeneity than inferred from measurements of expired gases at the mouth. The model analysis suggests that if anatomical data used are representative of a normal lung, then the intra-acinar gas inhomogeneity, although substantial, constitutes a small fraction of the overall impairment in gas mixing.