This is a randomized, controlled, phase II clinical trial to evaluate the efficacy, safety and immunogenicity of the apical membrane antigen-1 of Plasmodium (P.) falciparum (AMA-1) malaria vaccine FMP2.1/AS02A using rabies vaccine as a control in healthy children 1-6 years old in Bandiagara, Mali. This study is linked to DMID protocol 05-0146, which is a phase I dose escalation trial at the same site in the same population. In this study, 400 subjects will be randomized in a 1:1 ratio to receive either 50 micrograms of FMP2.1 in 0.5 mL AS02A or rabies vaccine. Immunizations will be given on days 0, 30 and 60. Solicited adverse events will be recorded on the days of immunization and at 1, 2, 3 and 7 days after each immunization. Unsolicited adverse events will be recorded for 30 days after each immunization. Passive case detection will be used to capture clinical malaria episodes and adverse events including serious adverse events, and will occur by continuous availability of clinical care in a population with high utilization of this care. Active surveillance will be used to capture malaria infections and adverse events including serious adverse events. For active case detection, following the third dose, participants will be followed monthly for 6 months and then at 12, 18 and 24 months after randomization, for clinical assessment, malaria smear and hemoglobin. Routine monthly malaria smears will not be read immediately unless symptoms are present. Children will be followed for 2 years after the first immunization. Sera will be collected for anti-FMP2.1 antibody titers on the days of immunization and 1, 3, 6, 8, 12, 18 and 24 months after the first immunization. Peripheral blood mononuclear cells (PBMCs) will be collected on the days of immunization, 30 days after the third immunization and 8, 12, 18 and 24 months after the first immunization. The study Final Report will be based on data collected up to 6 months after the assigned date of the third immunization. A supplemental report will include data from the entire 24-month observation period. Primary study objectives are to: determine the efficacy of FMP2.1/AS02A in children aged 1-6 years against first clinical malaria episodes (axillary temperature of greater than or equal to 37.5 degrees Celsius and parasitemia of greater than or equal to 2500/mm\^3) occurring between randomization and 6 months after the assigned date of the third immunization; and assess the safety of the vaccine in children aged 1-6 years. Secondary study objectives are to: describe the dynamics of anti-AMA-1 antibody responses in recipients of the malaria vaccine compared to natural responses in the control group; determine whether serum anti-AMA-1 IgG titer by enzyme linked immunosorbent assay (ELISA) 1 month after the third immunization correlates with protection against clinical malaria episode; measure allele-specific efficacy against parasites with AMA-1 genotypes homologous to and heterologous to the 3D7 clone of P. falciparum; determine vaccine efficacy against clinical malaria episodes occurring between randomization and 6 months after the assigned date of the third immunization; and if efficacy is observed based on the primary endpoint, to determine vaccine efficacy against first clinical malaria episode and all clinical episodes (using increasing parasitemia thresholds) occurring during 2 years after randomization.