['The underlying mechanism for the increased alveolar-arterial oxygen tension difference resulting from almost all forms of general anesthesia is unknown. We hypothesized that inhalation anesthesia influences the intrapulmonary distribution of ventilation (V) and perfusion (Q), leading to less advantageous V/Q matching.', 'Ten healthy volunteers were studied in supine position on two separate occasions, once awake and once during mild anesthesia (sevoflurane inhalation) with maintained spontaneous breathing. On both occasions, the distribution of V and Q were simultaneously imaged using single photon emission computed tomography. V was tagged with [Tc]-labeled carbon particle aerosol and Q with [In]-labeled macroaggregates of human albumin. Atelectasis formation during anesthesia was prevented using low concentrations of oxygen in inhaled air.', 'Mean V and Q distributions in the ventral-to-dorsal direction, measured in 20 equally spaced volumes of interest and in three regions of interest of equal volume, did not differ between conditions. Anesthesia, when compared with the awake state, significantly decreased the total heterogeneity of the Q distribution (P = 0.002, effect size 1.16) but did not alter V (P = 0.37, effect size 0.41). The corresponding V/Q total heterogeneity was higher under anesthesia (P = 0.002, effect size 2.64). Compared to the awake state, the V/Q frequency distribution under anesthesia became wider (P = 0.009, 1.76 effect size) with a tendency toward low V/Q ratios.'] Does inhalation anesthesia increase V/Q regional heterogeneity during spontaneous breathing in healthy subjects?