The diagnosis of occupational asthma is usually performed in epidemiology using a combination of symptoms and bronchial hyperresponsiveness, while in a clinical setting the 'gold standard' for the diagnosis of occupational asthma is the specific bronchial challenge test in the laboratory The aim of this study was to detect new cases of flour-induced occupational asthma (OA) in a group of workers exposed to grain and/or flour dust, by means of a step-by-step approach, as used in a clinical setting. In an epidemiological study, III millers and 186 bakers were examined by means of questionnaire, pulmonary function tests and skin-prick tests (SPT) to common allergens and to wheat flour dust extracts. From the whole sample, 82 subjects who showed asthma-like symptoms in the questionnaire and/or low forced expiratory volume in 1 sec (FEV1) were selected. Selected subjects underwent methacholine challenge test, and hyperreactive subjects underwent specific bronchial challenge with flour dust in the laboratory. Sixty-two of the selected subjects performed the methacholine challenge test, and 22 (33 8%) were hyperreactive (PD20 FEV1 <1 mg of methacholine). Fifteen of 22 hyperreactive subjects underwent specific bronchial challenge test (s BCT) with flour dust; a positive response was elicited in six subjects. These subjects can be diagnosed as having flour-induced occupational asthma. Atopy and skin sensitivity to flour was partially related to the response to flour bronchial challenge. Bronchial hyperreactivity can be observed in a small percentage of subjects with asthma-like symptoms and/or low FEV1, and a positive response to s BCTwas observed in a subgroup of hyperreactive subjects.Therefore, using these selection criteria, a diagnosis of flour-induced OA, as commonly performed in a clinical setting, can be performed in few previously undiagnosed subjects.This approach could be relevant for an early diagnosis ofoccupational asthma.