We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation assays in vitro. Anti-GLURP and anti-Pf155/RESA antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and erythrocyte membrane immunofluorescence (EMIF), and total anti-P. falciparum antibodies were measured by indirect fluorescent antibody test (IFAT). Immunological reactivities were evaluated every six months, at the end of the rainy season and at the end of the dry season, both during the period of chemoprophylaxis and during the follow-up. The antibody response rate to the GLURP was lower in the Maloprim group than in the placebo group during the intervention phase. The lymphoproliferative response rate to the malaria antigens was significantly lower at the end of the rainy season than at the end of the dry season, but the difference between the experimental group and the control group of schoolchildren was not statistically significant. These results suggest that the antibody responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria vaccine.