Plastic is increasing in abundance in nearly every possible aquatic environment worldwide. Once in an aqueous environment, plastic can release estrogenic additives and toxic sorbed contaminants to biota via leaching and ingestion. Ultra-violet (UV) radiation and saltwater can enhance the desorption of additives and contaminants. Additionally, plastic can release chemicals at enhanced quantities under gut conditions. Plastic’s ability to cause harm to fish through the leaching of additives and sorbed contaminants in a highly plastic-polluted sensitive estuarine environment was investigated using in vitro and in vivo bioassays and targeted chemical analysis. Ocean-recovered and UV-irradiated plastic released leachates that were biologically active in larval Japanese medaka (Oryzias latipes) fish, with confirmation of estrogenic and aryl hydrocarbon receptor activity in vitro as well as targeted analytical chemistry. Plastic’s ability to transfer estrogenic additives via ingestion was investigated by simulating the digestion of plastic for fish, seabird and invertebrates using a range of plastic sizes and types. All simulated gut conditions enhanced the desorption of estrogenic plastic additives, with smaller sizes desorbing greater quantities from polystyrene. Estrogenic activity of plastic gut extracts, as measured using a quantitative in vitro bioassay, correlated poorly with chemical estimates of estrogenicity, suggesting that non-targeted chemicals may be responsible for the biological activity. Finally, the ability of plastic to transfer the cardiotoxic and visually-impairing pollutant benzo(a)pyrene (BaP) to developing pelagic fish species was examined. Juvenile White seabass (Atractoscion nobilis) that ingested BaP-sorbed polystyrene over 5 days did not display significant signs of exposure to BaP through the measurement of enzyme activity nor through behavioral assays designed to detect impairments in visual function. Results from these experiments suggest that plastic may cause harm to biota through the release of estrogenic plastic additives through various routes of exposure, including aqueous dermal uptake and ingestion. The transfer of adsorbed toxic contaminants to fish through ingestion of micron-sized polystyrene may not be of high concern due to the lack of significant effects observed in exposed White seabass fish.