Although T helper 2 (Th2) cytokines are known to be critical in the generation of protective immunity against intestinal helminths in mouse models, it is unclear whether they are important in natural immunity against gut helminthiases in humans. Therefore, we investigated cytokine production in ex vivo whole-blood cultures in response to Ascaris lumbricoides antigen and mitogen in a cross-section of a community where the parasite is hyperendemic. The intensity of A. lumbricoides infection was significantly reduced after age 11 years. Levels of cytokines associated with Th2 lymphocytes (interleukin [IL]–4, IL-9, IL-10, and IL-13) demonstrated an inverse relationship with intensity of A. lumbricoides infection only in individuals aged >11 years. Furthermore, the IL-9, IL-10, and IL-13 produced in response to parasite antigen were of primary importance in this relationship. These findings promote a role for Th2-mediated responses in the age-dependent reduction of intestinal helminth infections in humans