It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L-1; p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship. Copyright©ERS 2013.