We conducted a matched case-control study to assess the association between epidemic asthma and soybean sensitivity in Cartagena, Spain. In skin tests, 81% of the cases and no control subjects were positive to the commercial soybean allergen; 87% of the cases and 12% of the controls were positive to the prepared soybean allergen; and 69% of the cases and 6% of the controls showed high levels of specific immunoglobulin E antibodies (odds ratio = 10; 95% confidence interval = 1.4-433). The association remained strong after adjustment for total immunoglobulin E and for 28 other allergens. The results indicate that soybean sensitivity may be causing asthma epidemics in Cartagena.