Laboratory animal (LA) workers are frequently affected with allergic sensitization and occupational asthma (OA). The role of preexposure host factors, in particular airway responsiveness, on the incidence of OA has not been satisfactorily studied. A prospective cohort study of 417 apprentices in animal-health technology was conducted to investigate the incidence and determinants of probable OA. Questionnaire and skin-prick tests with common and work-specific allergens were administered on entry and at follow-up visits (up to three) from 8 to 44 mo after starting apprenticeship. Responsiveness to inhaled methacholine was assessed at baseline and at follow-up in apprentices who developed a new specific skin sensitization and in control subjects. Preexposure host characteristics and the school attended were compared between cases and all cohort subjects not meeting the criteria for probable OA. Twenty-eight apprentices satisfied the definition for probable OA, i.e., onset of immediate skin reactivity to > 1 occupational inhalant and > 3.2-fold decrease in the provocative concentration causing a 20% reduction in FEV(1) (PC(20)). The incidence of probable OA was 2.7% (28/1,043 person-years). Baseline immediate skin reactivity to pets (rate ratio [RR] 4.1, 95% confidence interval [CI] = 1.6 to 10.8), and bronchial responsiveness (PC(20) < or = 32 versus PC(20) > 32 mg/ ml) (RR = 2.5, 95% CI = 1.0 to 5.8) were associated with an increased risk of probable OA; a lower FEV(1) had an apparent, protective effect (RR = 0.58, 95% CI = 0.43 to 0.78). It is concluded that apprentices in animal health show a high incidence of probable OA, and that preexposure airway caliber and responsiveness as well as sensitization to pets are associated with an increased risk.