A randomized, double-'blind', placebo-controlled trial of weekly Maloprim (dapsone-pyrimethamine, D-P) for malaria prophylaxis was conducted at Magoda village in north-eastern Tanzania. The effect of D-P on the incidence of clinical malaria, Plasmodium falciparum prevalence and density, splenomegaly, and packed cell volume (PCV) was investigated in a cohort of 249 children (126 receiving D-P and 123 receiving placebo) aged 1-9 years. The case definition of clinical malaria (malaria fever) was measured axillary temperature > or = 37.5 degrees C and/or reported fever, and P. falciparum asexual parasitaemia > or = 5000/microL. Children aged 1-4 years given D-P experienced 1.56 episodes of clinical malaria per year, whereas children on placebo experienced 2.55 episodes (relative rate [RR] = 0.61, 95% confidence interval [CI] 0.47, 0.80). Thus, D-P protective efficacy against clinical malaria, in this age group, was 39% (95% CI 20%, 53%; P = 0.0002). The annual incidence of clinical malaria among children aged 5-9 years was 0.16 episodes in the D-P group and 0.26 episodes in those receiving placebo (RR = 0.58, 95% CI 0.26, 1.28; P = 0.17). Increased malaria transmission and drug resistance, during the course of the trial, resulted in a reduction in the protective efficacy of D-P. Overall, D-P was able to reduce parasite densities and splenomegaly. D-P prophylaxis also resulted in an increase in PCV but this effect diminished towards the end of the trial. D-P exerted a suppressive effect on asexual parasitaemia throughout the trial.