Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS-DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40-72% of examined subjects, workplace-related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12-25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace-related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specificity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace-related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace-related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenges test result. Hence, the MC test can reduce performance of the laborious specific challenge test.