The Río Pilcomayo heads on the Cerro Rico de Potosí precious metal-polymetallic tin deposits of Southern Bolivia. Mining of the Potosí deposits began in 1545 and has led to the severe contamination of the Pilcomayo's water and sediments for at least 200 km downstream of the mines. This investigation addresses the potential human health affects of metal and As contamination on four communities located along the upper Río Pilcomayo by examining the potential significance of human exposure pathways associated with soils, crops and water (including river, irrigation and drinking water supplies). The most significantly contaminated agricultural soils occur upstream at Mondragón where Cd, Pb and Zn concentrations exceed recommended guideline values for agricultural use. Further downstream the degree of contamination decreases, and metal concentrations are below Dutch, German and Canadian guideline values. Metal and As concentrations in agricultural products from the four communities were generally below existing guidelines for heavy metal content in commercially-sold vegetables. Thus, the consumption of contaminated produce does not appear to represent a significant exposure pathway. A possible exception is Pb in carrots, lettuce and beetroots from Sotomayor and Tuero Chico; 37% and 55% of the samples, respectively, exceeded recommended guidelines. Most communities obtain drinking water from sources other than the Río Pilcomayo. In general, dissolved concentrations of metals and As in drinking water from the four studied communities are below the WHO guideline values with the exception of Sb, which was high at Tasapampa. The inadvertent ingestion of contaminated water from irrigation canals and the Río Pilcomayo represents a potential exposure pathway, but its significance is thought to be minimal. Given the degree of soil contamination in the area, perhaps the most significant exposure pathway is the ingestion of contaminated soil particles, particularly particles attached to, and consumed with vegetables. The risks associated with this pathway can be reduced by thoroughly washing or peeling the vegetables prior to consumption. Other exposure pathways that are currently under investigation include the consumption of contaminated meat from livestock and poultry, which drink polluted waters and the ingestion of contaminated wind-blown dust.