A cohort of 48 Gambian children was protected against malaria by fortnightly administration of Maloprim (pyrimethamine and dapsone) for 2 years between their 3 and 5 birthdays. A matched cohort of 47 children received placebo. During the year following the termination of prophylaxis there was no increase in the frequency of clinical attacks of malaria in the protected children compared with the control children. Antibody levels to circumsporozoite protein were measured by a radioimmunoassay and that to blood-stage antigens by a variety of techniques including an ELISA to whole blood-stage Plasmodium falciparum antigen, immunofluorescent assays (IFAT) to acetone fixed, glutaraldehyde fixed and unfixed parasites, a merozoite inhibition test and an opsonizing assay. Antibody levels were, in general, lower in protected than in control children and several differences between the two groups were statistically significant. When antibody levels were measured by ELISA and IFAT at the end of the following rainy season, when malaria transmission was intense, those in protected children had increased to comparable levels to those found in control children. Our findings suggest that chemoprophylaxis given for 2 years lowers malaria antibody levels but that it does not interfere with the development of protective immunity.