Frontier malaria is a biological, ecological, and sociodemographic phenomenon operating over time at three spatial scales (micro͞ individual, community, and state and national). We explicate these linkages by integrating data from remote sensing surveys, groundlevel surveys and ethnographic appraisal, focusing on the Machadinho settlement project in Rondô nia, Brazil. Spatially explicit analyses reveal that the early stages of frontier settlement are dominated by environmental risks, consequential to ecosystem transformations that promote larval habitats of Anopheles darlingi. With the advance of forest clearance and the establishment of agriculture, ranching, and urban development, malaria transmission is substantially reduced, and risks of new infection are largely driven by human behavioral factors. Malaria mitigation strategies for frontier settlements require a combination of preventive and curative methods and close collaboration between the health and agricultural sectors. Of fundamental importance is matching the agricultural potential of specific plots to the economic and technical capacities of new migrants. Equally important is providing an effective agricultural extension service.Brazilian Amazon ͉ frontier malaria E conomically and politically driven human migration in the Amazon basin of Brazil over the past century has been accompanied by substantial ecosystem transformation and the promotion of malaria transmission (1-3). Research programs in parasitology, entomology, and epidemiology of vector-borne diseases were established in Brazil in the 1890s (4-6) followed, almost immediately, by translation into malaria mitigation strategies (3, 7). Major eradication and control campaigns in Amazonia, initiated in the 1950s and persisting until 1970 (1), succeeded in reducing the number of malaria cases in the region to Ϸ30,000 (in 1970) (roughly 60% of all cases reported in the country).The modern era of Amazon frontier expansion began during the military government with the introduction of large scale colonization projects focused on agriculture, mineral extraction, and wide-ranging human settlement (8-13). The human population of the Amazon grew from 7.2 million in 1970 to 11 million in 1980 and then to 18.7 million by 1996, accompanied by a dramatic increase in malaria cases (14, 15). As of 1999, there were Ϸ600,000 malaria cases in Brazil, 99.7% of which were concentrated in the legal Amazon. The spatial distribution of these cases was very irregular, and a lack of spatially targeted mitigation strategies resulted in inefficient allocation of resources. In 1986, 60% of all malaria cases in the Amazon were concentrated in 58% of the municipalities, but 70% of the budget for malaria control was spent in municipalities with only 3% of the cases (16).Characterizing malaria risk in the rapidly transforming Amazon ecosystems requires considering biological and ecological phenomena acting at multiple spatial scales, juxtaposed with behavioral and economic conditions. In this regard, we adapt and add precis...