Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10–induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite-and allergen-specific CD4+ T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil]+ allergy [A]+) were compared with the responses to three appropriate control groups (Fil− A−[n= 13], Fil− A+[n= 12], Fil+ A−[n= 11]). The most important findings revealed that Fil+ A+ had marked (p< 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil+ A−. Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4+ T cells producing IL-4, IL-5, IL-2, and TNF-α in Fil+ A+ when compared with Fil+ A− patients, but also in the frequencies of polyfunctional Th2-like (CD4+ IL-4+ IL-5+ and CD4+ IL-2+ IL-4+ IL-5+ TNF-α+) cells. The Th2-associated responses seen in the Fil+ A+ group were correlated with serum IgE levels (p< 0.01, r= 0.5165 for IL-4; p< 0.001, r= 0.5544 for IL-5; and p< 0.001, r= 0.4901 for IL-13) and levels of circulating eosinophils (p< 0.0116, r= 0.5656) and their degranulation/activation products (major basic protein [p< 0.001, r= 0.7353] and eosinophil-derived neurotoxin [p< 0.01, r= 0.7059]). CD4+ responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response.