Several factors including early-life antibiotic usage have been implicated in the rising prevalence of allergic sensitization and asthma. A nested case-control study comparing antibiotic exposure of 37 sensitized children with recurrent wheeze (age 3-5 yr) and 37 non-sensitized children who had never wheezed was carried out within a population-based birth cohort (matching for age, sex, parental atopy, allergen exposure, and pet ownership). We collected data on antibiotic prescriptions during first 3 yr of life (timing, type, indication) from the primary care medical records. Significantly, more cases than controls received one or more antibiotic courses during the first year of life (92% vs. 70%, p = 0.04). The median time to first antibiotic course was shorter for the cases than the controls (6 vs. 8 months, p = 0.03). The total number of antibiotic receipts was greater amongst cases in each of the first 3 yr of life, but this reached significance only when the whole three-year period was considered (249 vs. 182 courses, p = 0.05). The increased ratio of antibiotic receipt in cases over controls was highest in the first year of life (1.32, 95% CI 0.99-1.78). Significantly more cases than controls were prescribed antibiotics for lower respiratory tract infection during the first 3 yr (p = 0.007), but not during the first year of life (p = 0.52). Antibiotics use by class was similar in the two groups. Our data support the hypothesis that early life exposure to broad-spectrum antibiotics may have a causative role in sensitisation and the expression of wheeze.