Convective dependent flow heterogeneities associated with airways proximal to the acini are the dominant cause of abnormal ventilation distribution during induced bronchoconstriction (Verbanck, S., D. Schuermans, A. Van Muylem, M. Paira, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83:1907-1916, 1997). We applied a morphometric model of the human lung to predict flow distributions among the acini during heterogeneous bronchoconstriction and relate these distributions to impairments in the mechanical properties of the lung. The model has an asymmetrical branching airway system. Heterogeneous constriction was invoked by defining an airway constriction distribution with a mean (mu) and coefficient of variation (CV) and either a Gaussian or log normal distribution. The lung resistance (RL) and elastance (EL) were most sensitive to severely heterogeneous constriction that produced a few highly constricted or closed airways dispersed randomly throughout the periphery. Ventilation distribution in the healthy lung was effectively homogeneous over the frequency range of 0.1-5.0 Hz. With homogeneous or mildly heterogeneous constriction (CV< or =20%) ventilation remained fairly homogeneous at low frequencies (< or =0.1 Hz) but rapidly became heterogeneous as frequency increased. Conversely, a low mean but severely heterogeneous constriction that produced random airway closure produced abnormal ventilation distribution in most acini at all frequencies, and some acini received up to 25 times the normal ventilation. This suggests that certain forms of heterogeneity can lead to shear induced lung injury even at common mechanical ventilation rates.