Patients with ASA-sensitive asthma form a clinically homogeneous subgroup of asthmatics characterized by nonatopic eosinophilia, sinusitis, nasal polyps, and frequent steroid dependency. Twenty-six Caucasian patients with ASA-sensitive asthma and 22 Caucasian patients with uncomplicated asthma were typed for HLA Class I and II antigens. A significant increase in HLA-DQw2 (relative risk, 4.06) was found in ASA-sensitive asthmatics. Asthmatic patients who were not ASA-sensitive had HLA frequencies that did not differ significantly from healthy Caucasian control subjects. These findings suggest that ASA-sensitive asthma represents a disease entity unique from other forms of asthma. Presumably, DQw2 or an associated genetic factor is involved in the pathogenesis of ASA-sensitive asthma.