Hypocapnia increases ventilation/perfusion (VA/Q) heterogeneity in dogs, possibly by adversely affecting distribution of ventilation through its effects on collateral ventilation. Because pigs lack collateral ventilation, we compared the effects of hypocapnia on ventilation heterogeneity in pentobarbital-anesthetized, mechanically-ventilated dogs and pigs. Simultaneous multiple breath washouts of helium and nitrogen were used to assess the uniformity of the ventilation distribution by the phase III (SnIII) method. Ventilation heterogeneity was partitioned into two components, e.g. convective-dependent inhomogeneity (cdi) and diffusive-convective-dependent inhomogeneity (dcdi). Pulmonary gas exchange was also measured in pigs by the multiple inert gas elimination technique. Ventilation heterogeneity was increased (P < 0.01) in hypocapnic dogs. Inspiration of CO2 decreased ventilation heterogeneity by decreasing dcdi (P < 0.01). In contrast, ventilation heterogeneity was not increased in hypocapnic pigs. However, hypocapnia increased VA/Q heterogeneity by 18% (P < 0.05) in pigs. We conclude that hypocapnia increases ventilation heterogeneity in dogs but not in pigs, most likely related to an interspecies difference in collateral ventilation.