Since 2000, CDC and the Ifakara Health Research and Development Centre (IHRDC), recently renamed Ifakara Health Institute (IHI) have operated a series of malaria control and research collaborations, leading directly to substantial gains in child survival across wide parts of southern Tanzania. This application proposes a revived implementation research agenda that will support malaria policy makers and other public health officials in Tanzania and throughout subSaharan Africa to address three important objectives: 1. to address the opimal mix of currently validated malaria control interventions across malaria transmission zones and diverse epidemiological and cultural settings. 2. to rapidly develop and validate the impact of revised, enhanced or novel interventions that will contribute to effective malaria control at scale. 3. to establish the most feasible and effective opportunities for integration with other US Government supported child survival, environmental health, vector control and infectious disease programs. Through an interdisciplinary research team and strong links with national and local health authorities, CDC and IHI/ IHRDC have already helped to establish a strong rational for universal distribution of insecticide treated bednets, a workable plan for deployment and quality assurance of rapid diagnostic tests for malaria, and established the first programmatic introduction of artemisinin containing combination therapies for malaria. We propose to build upon the partnership that was established to achieve these milestones and apply our attention to new and potentially life-sparing innovations such as improved detection of antimalarial drug resistance, enhanced guidelines for managing sick children without evidence of malaria infection, and maintaining our decades-long effort to document the reach and impact of malaria control and child survival interventions. Details of the research plan are outlined in the continuation pages.