An association of Chlamydia pneumoniae infection and reactive airway disease has been demonstrated in children. To determine if C. pneumoniae infection triggers production of C. pneumoniae-specific IgE, sera were examined from 45 children with and without C. pneumoniae infection. Anti-C. pneumoniae IgE was demonstrated by immunoblotting in 12 (85.7%) of 14 culture-positive asthmatic patients with wheezing compared with only 1 (9.1%) of 11 culture-positive patients with pneumonia, 2 (18.2%) of 11 culture-negative asthmatic children with wheezing, and 2 (22.2%) of 9 culture-negative asymptomatic patients. The most commonly recognized proteins were at 98 (82.4%), 78 (58.8%), 58-60 (70.6%), and 36 kDa (64.7%). The presence of anti-C. pneumoniae IgE by immunoblotting was not associated with the presence of anti-C. pneumoniae IgG and IgM by microimmunofluorescence. These results suggest that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection.