Epidemics of emergency room admissions for asthma occurring in Barcelona during the period 1981 to 1987 were caused by inhalation of soybean dust. To investigate the risk factors that determined why some asthma patients became reactive to soybean and were consequently affected by the asthma epidemics of Barcelona but others did not do so, a case-control study was conducted during 1989, 2 yr after the cessation of asthma epidemics. Patients with asthma admitted in emergency room services during epidemic asthma days (n = 169) were compared with asthma patients admitted in the same services during nonepidemic days and who were never admitted during the epidemics (n = 147). Risk factors other than soybean exposure, namely skin reactivity against at least one common allergen (odds ratio [OR] 3.0, 1.7 to 5.3), age over 64 yr (OR 2.8, 1.4 to 6.0), cigarette smoking at the time of the epidemics (OR 2.3, 1.2 to 2.4), past smoking (OR 1.8, 0.9 to 3.7), and total immunoglobulin E (IgE) higher than 100 IU/ml (OR 1.7, 1.0 to 3.0), were found independently related to epidemic asthma. The role of smoking was especially important for those who had a positive skin reaction and were exposed to soybean dust (OR 7.9, 1.8 to 36.0). In this group, a dose-response pattern with pack-years was observed (p less than 0.01). The present findings suggest a multifactorial process for epidemic asthma, in which atopy and cigarette smoking played an important synergistic role. This has a preventive potential for IgE-related asthma.