A retrospective study on reported malaria cases in the municipality (county) of Barcelos, Amazonas State, Brazil, was performed from 1992 to 2004, emphasizing the high endemic area along the Padauiri, an affluent of the Rio Negro. 16,795 cases were reported, 10,318 (61.4%) from the rural area and 6,477 (38.6%) from the urban area. Mean annual parasite index for the period was 136.7 per 1,000 inhabitants in the urban area and 613.6 per 1,000 in the rural area of Barcelos and 708.9 per 1,000 in the Padauiri area. In the latter area, two periods were considered: one epidemic, from 1992 to 1998, and the other post-epidemic, from 1999 to 2004. Comparing the two periods, the male/female ratio changed from 1.8 to 1.14, mean patient age from 17.9 to 14.8, proportion of Plasmodium falciparum cases from 51.9% to 23.7%, proportion of slides with low P. falciparum parasite density from 35.3% to 44.9%, and proportion of P. vivax from 24% to 35% (all these differences were statistically significant, with p < 0.05). The changes in the epidemiological pattern of malaria in the Padauiri area will be further elucidated through prospective studies.