A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin test reactivity to 10 common aeroallergens was measured using standard techniques. Atopic disease was defined as a history of hayfever and/or asthma concomitantly with a positive skin-prick test. Logistic regression showed that parental atopy (odds ratio [OR] = 1.98; 95% confidence interval [CI], 1.12, 3.49; p = 0.019) and wheezy bronchitis before the age of 2 years (OR = 3.13; 95% CI, 1.63, 6.01; p < 0.001) were predictors of atopic disease, the latter especially when predisposition to atopy was present (OR = 8.63; 95% CI, 3.64, 20.44; p < 0.001). Duration of breast-feeding was longer in subjects with atopic heredity (p = 0.017), whereas smoking exposure during pregnancy (p = 0.019) and in the 1st year of life (p = 0.018) was less prevalent. Wheezy bronchitis was equally frequent among subjects with and without atopic predisposition (p = 0.893). Wheezy bronchitis before the age of 2 years seems to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits.