Methacholine challenge studies are often conducted to diagnose asthma in patients with mild or intermittent respiratory symptoms when screening spirometry results are normal. We hypothesized that in patients with increased nonspecific bronchial hyperreactivity (NSB-HR), gas trapping might be present and that this information could be a factor in clinical decision making. To assess the relationship between gas trapping and NSBHR, we conducted a retrospective chart review of 500 patients who had undergone pulmonary function testing, including lung volume measurement and methacholine challenge. Measurements of airflow, lung volumes, and methacholine PC20 values were compiled and analyzed. FRC was determined by body plethysmography (FRCB) and by helium dilution (FRC-He). FRCB-FRC-He, RV (percent of predicted) RV/TLC, and RV/TLC (percent of predicted) were used as measures of gas trapping. RV% and RV/TLC% were the best predictors of a PC20 < or = 8 mg/mL. In the subset of 169 patients who had FEV1/FVC > or = 90% of pred, an RV/TLC% value of 125% of predicted or greater had a positive predictive value of 62.5% and a negative predictive value of 62.0%. RV/TLC% was the only measure of gas trapping that was associated with a PC20 < or = 8 mg/mL (p < 0.05). Linear regression revealed no correlation between any measure of gas trapping and quantified PC20 value (< or = 16 mg/mL). These results suggest that patients with a normal FEV1/FVC who show gas trapping have an increased likelihood of a positive methacholine challenge study. Furthermore, in these patients, RV/TLC (percent of predicted) is the best predictor of a positive methacholine challenge and this parameter may be useful in raising the clinical suspicion of asthma in the large population of patients presenting with respiratory symptoms and normal flow rates.