Arterial oxygen tension (PaO2) is known to decrease with age, and this is accompanied by a number of changes in mechanical properties of the lungs, including loss of elastic recoil and increase in closing volume. The changes in respiratory mechanics with age could induce greater ventilation/perfusion (VA/Q) mismatch and thus explain the decrease in PaO2. In 64 normal subjects aged 18 to 71 yr (lifetime nonsmokers with normal spirometry), we measured VA/Q inequality and arterial respiratory blood gases (PaO2 and PaCO2) at rest in the seated position. VA/Q mismatch, represented by the second moments of the blood flow and ventilation distributions (log SDQ and log SDV) increased with age, but only slightly (mean log SDQ was 0.36 at age 20 yr and 0.47 at age 70 yr). PaO2 fell by a correspondingly small amount of 6 mm Hg. Previously established upper 95% confidence limits for log SDQ (0.60) and log SDV (0.65) in subjects at age 20 yr were confirmed. At age 70 yr, the upper limits of reference for log SDQ are 0.70 and for log SDV 0.75. The study shows that an increased alveolar-arterial O2 gradient with age is due to VA/Q inequality rather than to shunting.