Decreased serum cortisol levels have been proposed to contribute to nocturnal airway obstruction. We investigated whether endogenous cortisol levels are lower, and also whether the 24-h cortisol variation is greater, in children with asthma than in control subjects and assessed the relationship between serum cortisol and nocturnal airflow limitation in children with asthma. Cortisol and FEV(1) were measured every 4 h over 24 h; blood eosinophils, airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured at 0400 and 1600. Children with asthma had lower cortisol levels than did control subjects; at midnight the difference was significant. Subjects with nocturnal asthma (24-h FEV(1) variation > or =15%) had significantly lower cortisol levels than did control subjects at 0000, 0800, and 1200. A higher mean 24-h cortisol level in subjects with asthma was associated with a significantly higher FEV(1) as a percentage of the predicted value (FEV(1) %pred) at 0400, 0800, and 2000, yet not in control subjects. Higher 24-h cortisol variation was associated with lower FEV(1) %pred at all time points in both control subjects and subjects with nonnocturnal asthma. There was no significant association between the level or variation of cortisol and PD(20) methacholine (provocative dose of methacholine causing a 20% fall in FEV(1)), PD(20) AMP, or eosinophils. Our data suggest that lower cortisol levels contribute to both overall lower levels of FEV(1) especially at night. This may be due to a lack of suppression of airway inflammation.