Background Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE-sensitized children also produce strong IgG responses to the respective airborne molecules. Objective We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood. Methods We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid-Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kUA /L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively. Results The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% ± 13%; 61 ISAC Standardized Units ISU, 95% CI, 52.5-71.5 ISU), intermediate for vegetable food (48% ± 27%; 13 ISU 95% CI, 11.2-16.1 ISU), and lowest for airborne allergens (24% ± 20%; 3 ISU 95% CI, 2.4-3.4 ISU; P for trend < .001 for percentages, P  for trend < .001 for levels). IgG4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years. Conclusion The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG4 isotype.