Five women and three men, all obese and weighing 95 to 140 kg, were studied by routine pulmonary function tests and by a radioactive xenon technique, while seated upright at rest, to measure the regional ventilation and perfusion distribution in the lung. In four subjects in whom the expiratory reserve volume averaged 49% of predicted normal, the ventilation distribution as measured with (133)xenon was normal. In the remaining four subjects, in whom the expiratory reserve volume was reduced to less than 0.4 L and averaged only 21% of predicted values, the distribution of a normal tidal breath was predominantly to the upper zones. In all subjects the perfusion distribution was predominantly to the lower lung zones but was slightly more uniform than in normal nonobese subjects. During tidal-volume breathing, therefore, in four subjects the ventilation and perfusion distribution was substantially normal, whereas in the remaining four perfusion was maximal in the lower zones, to which ventilation was significantly reduced. These findings show that there may be significant ventilation/perfusion abnormality on a regional basis in obese subjects, this abnormality bearing a close relationship to the reduction in expiratory reserve volume, a finding predictable from recently published data on normal nonobese subjects (1). The abnormalities of ventilation/perfusion relationships that were demonstrated in four of the eight obese subjects could cause a reduction in arterial oxygen tension during resting tidal ventilation.