Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO.) was measured in the expired gas of children with asthma. Vital capacity expirates from 21 control subjects and 13 subjects with asthma were assayed by chemiluminescence. Measurements were highly reproducible (coefficient of variation, 2.6% +/- 1.1%) and did not vary with age, sex, height, or weight. Patients with asthma had mean NO. levels (16.3 parts per billion) that were more than threefold higher than those of control subjects (5.05 ppb; p < 0.001). Expired NO. decreased as airflow obstruction improved during corticosteroid treatment (r2 = 0.77; n = 7; p < 0.001) but remained higher than normal (13.5 ppb; n = 5; p < 0.01) even after airflow obstruction resolved. We demonstrate the use of a reproducible test for asthma in children that is independent of measures of airflow obstruction. We speculate that expired NO assays may prove to be a more sensitive measure of childhood asthma than spirometry.