Fifty-two Gambian children who had received fortnightly chemoprophylaxis with maloprim, (pyrimethamine and dapsone), and 45 receiving placebo, were studied. Cellular immune responses to malaria antigens, measured by lymphoproliferative responses and interferon production, were higher in children who had received prophylaxis than in controls, although the anti-malarial antibody levels were lower. During a one-year period after termination of prophylaxis, there was no increase in the frequency of clinical episodes of malaria in the children who had received Maloprim. These results suggest that chemoprophylaxis for 3 years may lower malaria antibody levels, but does not interfere with the development of protective immunity, perhaps by enhancing cell-mediated immune responses to malaria in protected children.