KL-6 is a useful marker for interstitial pneumonia of various origins. However, the role of KL-6 in common pediatric respiratory infections is largely unknown. In order to determine whether the KL-6 level is elevated during respiratory infection, and whether KL-6 is a useful biomarker for the disease activity, we evaluated serum KL-6 levels in 132 children with various respiratory infections. KL-6 levels were significantly higher in patients with measles, influenza, or respiratory syncytial virus infection than in the control subjects. On the other hand, KL-6 levels in patients with bacterial infections such as mycoplasma, chlamydia, or pertussis were comparable to the control values. In patients with viral infections, high KL-6 levels, as defined by the mean plus 2 standard deviations of the control group, significantly correlated with low SpO(2) or days of O(2) administration, but did not correlate with C-reactive protein or white blood cell counts. These results indicate that measurement of serum KL-6 levels is helpful for the management of common pediatric respiratory infections.