The role of repeated infections early in life in the development of childhood asthma and allergies has not been clarified. The aim of this study was to investigate the effect of repeated episodes of fever and antibiotic treatments during the first years of life on the prevalence of asthma, bronchial hyperresponsiveness (BHR), and atopy at school age in a representative population. Random samples of schoolchildren aged 5-7 yrs (n=7,545) and 9-11 yrs (n=7,498) were studied using the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. To assess the prevalence of disease and early childhood exposures, parental questionnaires were administered (response rates 82.2% and 85.3%, respectively). In addition, children underwent skin prick tests, hypertonic saline challenge and blood sampling for the measurement of serum immunoglobulin (Ig)E. Repeated episodes of fever and antibiotic treatment in early life were strongly associated with the prevalence of asthma (odds ratio (OR)=7.95; 95% confidence interval (CI) 6.02-10.50) and current wheeze at school age. Within asthmatic children the number of fever episodes and antibiotic courses were strongly inversely related to the prevalence of atopy (OR=0.25; 95% CI 0.11-0.54 for skin test reactivity) and BHR (OR=0.31; 95% CI 0.10-0.92). Furthermore, asthmatic children with recurrent early childhood infections were at a lower risk of being symptomatic at school age. When considering atopic and nonatopic asthmatic children separately, the highest risk of asthma with repeated early childhood infections was found for nonatopic asthma (OR=24.29; 95% Cl 11.86-49.76). These findings suggest that a subgroup of children with a triggering or inducing of asthmatic symptoms through repeated early childhood infections exists within the "asthma syndrome" which has a better prognosis and is less related to the atopic phenotype.