Background Environment may have a key role in the development of the immune system in childhood and environmental exposures associated with rural residence may explain the low prevalence of allergic and autoimmune diseases in the rural tropics. We investigated the effects of urban versus rural residence on the adaptive immune response in children living in urban and rural areas in a tropical region of Latin America.Methods We recruited school children in either rural communities in the Province of Esmeraldas or in urban neighborhoods in the city of Esmeraldas, Ecuador. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Peripheral blood leukocytes (PBLs) in whole blood were stimulated with superantigen, parasite antigens and aeroallergens and IFN-γ, IL-5, IL-10, IL-13, and IL-17 were measured in supernatants.Results We evaluated 440 school children; 210 living in rural communities and 230 in the city of Esmeraldas. Overall, urban children had greater access to piped water (urban 98.7 % vs. rural 1.9 %), were more likely to have a household bathroom (urban 97.4 % vs. rural 54.8 %), and were less likely to be infected with soil-transmitted helminth infections (urban 20.9 % vs. rural 73.5 %). Generally, detectable levels of cytokines were more frequent in blood from children living in urban than rural areas. Urban residence was associated with a significantly greater frequency of IL-10 production spontaneously (adjusted OR 2.56, 95 % CI 1.05-6.24) and on stimulation with Ascaris (adj. OR 2.5, 95 % CI 1.09-5.79) and house dust mite (adj. 2.24, 95 % CI 1.07-4.70) antigens. Analysis of effects of environmental exposures on SEB-induced IL-10 production within urban and rural populations showed that some environmental exposures indicative of poor hygiene (urban – higher birth order, A. lumbricoides infection; rural - no bathroom, more peri-domiciliary animals, and living in a wood/bamboo house) were associated with elevated IL-10.Conclusions In our study population, the immune response of children living in an urban environment was associated more frequently with the production of the immune regulatory cytokine, IL-10. Some factors related to poor hygiene and living conditions were associated with elevated IL-10 production within urban and rural populations. Keywords: Environment, Hygiene, Cytokine profile, Rural, Urban, Tropical Latin America