The hypothesis that repeated treatments enhance acquired immunity against schistosomes by stimulating strong T helper 2 responses was tested. Schistosoma haematobium-infected schoolchildren were monitored for 3 years. During the first 2 years, children who did not receive chemotherapy were compared with those treated once or repeatedly. After specific immune responses were measured at 24 months, praziquantel was given to all children to clear any schistosome infections. Twelve months later, the infection status of the children was determined and compared with cytokine profiles at month 24, to gain insight into which immunologic profiles can predict resistance or susceptibility to schistosome infections. Repeated treatment led to high specific levels of interleukin (IL)-5 and low interferon-gamma production but did not protect against reinfection. After adjusting for variables, such as sex, age, and infection status at study onset, high levels of parasite-specific IL-10 were a risk factor for reinfection, and high levels of IL-5 were associated with hematuria development.