Airway lengthening after pneumonectomy (PNX) may increase diffusive resistance to gas mixing (1/D_G); the effect is accentuated by increasing acinar gas density but is difficult to detect from lung CO-diffusing capacity (DL_CO). Because lung NO-diffusing capacity (DL_NO) is three- to fivefold that of DL_CO, whereas 1/D_G for NO and CO are similar, we hypothesized that a density-dependent fractional reduction would be greater for DL_NO than for DL_CO. We measured DL_NO and DL_CO at two tidal volumes (VT) and with three background gases [helium (He), nitrogen (N₂), and sulfur hexafluoride (SF₆)] in immature dogs 3 and 9 mo after right PNX (5 and 11 mo of age). At maturity (11 mo), background gas density had no effect on DL_NO, DL_CO, or DL_NO-to-DL_CO ratio in sham controls. In PNX animals, DL_NO declined 25-50% in SF₆ relative to He and N₂, and DL_NO/DL_CO declined ~50% in SF₆ relative to He at a VT of 15 ml/kg, consistent with a significant 1/D_G. At 5 mo of age, DL_NO/DL_CO declined 25-45% in SF₆ relative to He and N₂ in both groups, but DL_CO increased paradoxically in SF₆ relative to N₂ or He by 20-60%. Findings suggest that SF₆, besides increasing 1/D_G, may redistribute ventilation and/or enhance acinar penetration of the convective front.