The Andean Amazon has gained world renown for its remarkable biodiversity, high levels of endemism, native human communities, aesthetic beauty, and its hydrologic role as the headwaters of the world’s largest river system.  Although a significant human presence has existed for centuries, recent industrialization, exploitation of natural resources, and human population growth exert an increasing influence on the landscape and its rivers.  This research examined how water quality reflects both natural factors and a growing human presence in the Upper Pastaza River Basin, Ecuador.  Through a one-month synoptic sampling campaign, we quantified general water quality parameters, dissolved heavy metals, and major nutrients at 88 sites.  We also sampled macroinvertebrates at 13 sites to further characterize stream condition.  Results indicate higher concentrations of heavy metals, organic and inorganic nutrients, total suspended solids and total dissolved solids in streams draining headwater areas with dense human populations.  Further downstream, contaminant concentrations in the mainstem Pastaza River are diluted by tributaries draining low-impact catchments.  Planned hydroelectric projects may alter these dilution processes in the future.  Presently, there is a strong need for an integrated approach to water resources management in the Pastaza and other Andean Amazon basins.