Background: Malaria constitutes a major cause of morbidity in the Brazilian Amazon where an estimated 6 million people are considered at high risk of transmission. Indigenous peoples in the Amazon are particularly vulnerable to potentially epidemic disease such as malaria; notwithstanding, very little is known about the epidemiology of malaria in Indian reservations of the region. The aim of this paper is to present a spatial analysis of malaria cases over a four-year time period (2003 2006) among indigenous peoples of the Brazilian State of Rondônia, southwestern Amazon, by using passive morbidity data (results from Giemsa-stained thick blood smears) gathered from the National Malaria Epidemiologic Surveillance System databank. Results: A total of 4,160 cases of malaria were recorded in 14 Indian reserves in the State of Rondônia between 2003 and 2006. In six reservations no cases of malaria were reported in the period. Overall, P. vivax accounted for 76.18 of malaria cases reported in the indigenous population of Rondônia. The P. vivax/P. falciparum ratio for the period was 3.78. Two reserves accounted for over half of the cases reported for the total indigenous population in the period Roosevelt and Pacaas Novas with a total of 1,646 (39.57%) and 1,145 (27.52%) cases, respectively. Kernel mapping of malaria mean Annual Parasite Index API according to indigenous reserves and environmental zones revealed a heterogeneous pattern of disease distribution, with one clear area of high risk of transmission comprising reservations of west Rondônia along the Guaporé-Madeira River basins, and another high risk area to the east, on the Roosevelt reserve. Conclusion: By means of kernel mapping, it was shown that malaria risk varies widely between Indian reserves and environmental zones defined on the basis of predominant ecologic characteristics and land use patterns observed in the southwestern Brazilian Amazon. The geographical approach in this paper helped to determine where the greatest needs lie for more intensively focused malaria control activities in Indian reserves in the region. It also provided a reference to assess the effectiveness of control measures that have been put in place by Brazilian public health authorities.