Abstract. The specific serum IgG1, IgG4, and IgE responses to Dracunculus medinensis and the level of total IgE of individuals living in a highly endemic area of northern Ghana were measured by ELISA. Sera were obtained in the high transmission season from individuals with prepatent, patent, or postpatent infection as well as from individuals from the same endemic area who claimed to have never had a patent infection (i.e., endemic normal individuals). Individuals with prepatent or postpatent infections responded with a significantly lower mean level of specific IgG1 and IgG4 compared with individuals with a patent infection, and with a significantly higher mean level of specific IgG1 and IgG4 compared with endemic normal individuals. For specific IgE, no differences were found in the mean antibody level between the infection status categories. Individuals with a patent infection had a significantly lower mean serum level of total IgE compared with prepatent, postpatent, and endemic normal individuals. Endemic normal individuals had the highest mean level of total IgE. Furthermore, in all clinical categories, high responders for specific IgG1 and IgG4 generally had low levels of total IgE, whereas low responders for specific IgG1 and IgG4 generally had high levels of total IgE. A similar dichotomy, although less distinct, was observed between specific IgG1 and IgG4 on the one hand and specific IgE on the other. Thus, similar to what has been suggested for schistosomiasis and lymphatic filariasis, the relationship between the IgG subclasses and IgE appears to play a role in, or at least to reflect, a mechanism for protective immunity in dracunculiasis.Human infections with Dracunculus medinensis (guinea worm) occur in parts of West and Central Africa and in Yemen and India. 1 The 10-12-month prepatent period is asymptomatic except for the last 1-2 weeks during which the adult female worm reaches subcutis and prepares for penetration of the body surface. At this late stage, the worm becomes palpable in the skin and a blister develops around its anterior end, thus making the patient aware of the infection. 2,3 Currently, no reliable method exists for diagnosis of dracunculiasis in the asymptomatic part of the prepatent period.Dracunculus medinensis induce vigorous humoral immune responses in infected individuals. 4-7 However, little is known about the relationship between the humoral responses and infection status (i.e., prepatent, patent, postpatent and those claiming to have never had a patent infection). Briefly, previous studies indicated that individuals in a prepatent and patent stage of infection responded similarly with total specific immunoglobulins, 4 and individuals in a patent and postpatent stage responded similarly with total specific immunoglobulins and specific IgG1, IgG4, and IgE. 5 Sera from endemic normal individuals (claiming to have never had a patent D. medinensis infection despite living in a highly endemic area) responded only weakly with specific IgG1 and IgG4 compared with individuals with...