To investigate the possible pathogenic role of food allergy in asthma, airway hyperresponsiveness was measured by methacholine inhalation challenges (MIC) performed before and after double-blind, placebo-controlled food challenges (DBPCFC) in 26 food-allergic, asthmatic patients. Airway hyperresponsiveness was classified as severe in two cases (PD20FEV1 < 2 breath units, BU), moderate in 18 (PD20FEV1: 2-20 BU), and mild in six (PD20FEV1 > 20 BU). Medications included albuterol (81%), inhaled steroids (38%), cromolyn (35%), and theophylline (23%). MICs were performed in the afternoon after DBPCFC. Of the 22 positive DBPCFC, 12 involved chest symptoms (cough, wheezing, or both). Another 10 positive DBPCFCs included laryngeal, gastrointestinal, and/or skin symptoms without any chest symptoms. Significant increases in airway hyperresponsiveness were evident in seven of 12 patients experiencing chest symptoms during DBPCFC. Significant increases in airway hyperresponsiveness were observed in one patient without chest symptoms during a positive DBPCFC and one patient after a negative DBPCFC. However, this last patient had a negative MIC with the same antigen 1 yr later. These studies indicate that food-induced allergic reactions can increase airway reactivity, and may do so without inducing acute asthma.