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Although high levels of fish consumption and bioindicators of mercury exposure have been reported for traditional populations in the Amazon, little is known about their actual daily intake of Hg. Using an ecosystem approach, calculate daily mercury intake in adult fish-eaters, examine the relations between mercury intake and bioindicators of exposure and the factors that influence these relations. A cross-sectional dietary survey on fish and fruit consumption frequency was carried out with 256 persons from six villages of the Tapajós River. Fish portion per meal was determined. Mercury concentration was determined for 1123 local fish specimens. Daily mercury intake (μg/kg/day) was determined for men and women from each village using the average fish-mercury concentration for the fish caught in their fishing zone, the average quantity of fish per meal, fish-species frequency consumption and participants’ body weight. Fish-mercury averaged 0.33 μg/g±0.33. Daily mercury intake varied between 0 and 11.8 μg/kg/day (mean 0.92 μg/kg/day±0.89) and varied by gender and village. Mean blood- and hair-mercury were 58.7±36.1 μg/l and 17.9±11.5 μg/g, respectively. There was a strong and positive relation between blood-mercury and daily mercury intake, with an inverse relation for fruit intake and schooling; significant variations were observed with immigrant status, and among villages. Hair-mercury was directly associated with daily mercury intake and inversely related to schooling and fruit consumption. Fruit consumption modified the relation between daily mercury intake and blood-mercury levels: for the same daily mercury intake, persons eating more fruit had lower blood-mercury concentrations (ANCOVA Interaction term: F=10.9, P<0.0001). The median difference of the ratio of blood-mercury to daily mercury intake between low and high fruit consumers was 26, representing a 26.3% reduction. These findings reveal high levels of daily mercury intake. Rigorous studies for developing risk-based reference doses in the Amazon should be undertaken to orient viable risk-management strategies to reduce exposure, while maintaining fish diet.Journal of Exposure Science and Environmental Epidemiology (2008) 18, 76–87; doi:10.1038/sj.jes.7500599; published online 5 September 2007 [ABSTRACT FROM AUTHOR]