Background: Lower prevalence rates for childhood respiratory allergies have been reported in eastern Germany than in western Germany. Objective: Because allergic phenotypes are thought to be associated with an unbalanced T_H1/T_H2 T cell effector response, a cross-sectional investigation was carried out as part of the German ISAAC Phase II study to determine whether T_H1/T_H2 capacity might have developed in different directions during the separation between the 2 parts of the country. Methods: In a community-based random sample of 9- to 11-year-old (n = 6399) and 5- to 7-year-old (n = 6202) children in eastern and western Germany, the prevalence of atopy was assessed. Heparinized blood samples were collected from a subgroup of children stratified according to the number of older siblings. T_H1 and T_H2 cytokine productivity was determined after stimulation with phorbol ester plus ionomycin. Results: Individuals who grew up in eastern Germany had a marked bias toward T_H0 responsiveness (>60%), regardless of whether they were atopic. In contrast, the children of western Germany, particularly when they were atopic, showed T_H2 polarization. Conclusions: This is the first epidemiologic survey to demonstrate regional differences in the T_H1/T_H2 response pattern and their relation to atopic disease between regions. (J Allergy Clin Immunol 2002;109:338-42.)