The hypotheses tested in this study were that during acute asthma exacerbations (1) exhaled nitric oxide concentrations [eNO] are a more sensitive, noninvasive indicator of asthma disease activity than serum markers of inflammation such as eosinophil cationic protein (ECP) or soluble interleukin 2 receptor (sIL2R), and (2) elevated [eNO] are reduced after treatment with glucocorticoids (GC). Peak eNO levels were measured by chemiluminescence during slow expiration. Seven asthmatic subjects (mean age 11 yrs; mean morning FEV1 65% predicted) receiving inhaled GC, and with no radiographic evidence of acute sinusitis, were studied before and after a course of oral GC. Measurements of [eNO], ECP and sIL2R levels, and FEV1% were obtained before and after a course of GC. Six atopic nonasthmatic subjects (mean age 12 years; mean FEV1 94% predicted) and seven normal subjects (mean age 13 years; mean FEV1 100% predicted) were studied. The mean peak [eNO] level (parts per billion: ppb) for the asthma subjects before treatment (52 +/- 5 ppb SEM) was greater than the value for both nonasthmatic atopic and normal subjects (16 +/- 2 ppb and 14 +/- 2 ppb SEM, respectively; P < 0.0001). There was no significant difference in ECP or sIL2R values between asthmatic subjects and either atopic or normal subjects (P > 0.05). Baseline pre-GC treatment ECP levels in the asthmatic subjects were significantly higher (P < 0.002) than post-GC treatment values. The mean peak [eNO] level in the asthmatic subjects declined after oral GC treatment to 14 +/- 1 ppb (P < 0.0002) and was less than 2 ppb different from either control group (P > 0.75). We conclude that [eNO] is a more sensitive marker of asthma disease activity than ECP and sIL2R levels. In addition, [eNO] appears to be a more useful indicator of the beneficial response to GC therapy than these other measurements in pediatric asthma.