Biological Response Indicator Devices Gauging Environmental Stressors (BRIDGES) is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, OR, USA. Six sampling events were conducted in the summer and fall of 2009 and 2010. Passive sampling device extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1,201 chemicals of concern using deconvolution-reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. The BRIDGES tool provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry-toxicity associations. Modeling elucidated spatial and temporal trends in PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although the present study highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples.