Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U x mL(-1) were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics. Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1)% predicted (66+20% versus 83+/-17%; p<0.001), FEV1% forced vital capacity (FVC) (70+/-14% versus 81+/-8%; p<0.001) and forced mid expiratory flow (FEF25-75) (1.7+/-0.9 L x s(-1) versus 2.8+/-0.9 L x s(-1); p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEVI % pred: r=-0.5, p<0.001; FEV1% FVC: r=-0.53, p<0.001; FEF25-75: r=-0.52, p150 U x mL(-1). These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity.