BACKGROUND: The effect of breastfeeding duration on subsequent asthma and allergy remains the subject of much controversy. OBJECTIVE: To investigate whether differences in study design or disease-related exposure modification were the cause of the differences in study findings. METHOD: The data from two cohorts, the Childhood Asthma Prevention Study (CAPS) from Australia and the Barn Allergi Miljo Stockholm cohort from Sweden, which had reported different findings on the association between breastfeeding and asthma, were combined. For this analysis, the definitions for breastfeeding, asthma, and allergy were harmonized. Subjects were included if they had at least one parent with wheeze or asthma and had a gestational age of more than 36 wks (combined n = 882). The risk of disease-related exposure modification was assessed using survival analysis. RESULTS: Breastfeeding reduced the risk of asthma at 4/5 and 8 yrs of age in children with a family history of asthma. The effect was stronger in the Swedish cohort. Breastfeeding had no effect on the prevalence of sensitization to inhaled allergens in this cohort with a family history of asthma but was a risk factor for sensitization to cow's milk, peanuts, and eggs in the CAPS cohort at 4/5 yrs and in the combined cohort at 8 yrs. There was no evidence to support the existence of disease-related exposure modification in either cohort. CONCLUSION: These findings point to the importance of harmonization of features of study design, including subject selection criteria and variable definitions, in resolving epidemiological controversies such as those surrounding the impact of breastfeeding on asthma and allergic sensitization.