The dewatering of New Orleans following Hurricane Katrina created an unprecedented situation regarding public safety, including the perception of unsafe seafood. The floodwaters flowing into nearshore areas of the Gulf of Mexico (GoM) were known to contain oils, metals, and a wide range of pathogens and enteric bacteria, and there was also concern about synthetic chemical contaminants from flooded businesses and homes. The Northwest Fisheries Science Center was asked to mount an immediate response, both to collect samples of fish and shrimp from the potentially affected area as well as providing a wide range of chemical and microbiological analyses. Consequently, we conducted several sampling cruises from a variety of research vessels and chartered fishing boats in the GoM over the course of the following 12 months. While we sampled many species, we focused our analyses on Atlantic croaker Micropogonias undulalus and white shrimp Litopenaeus setiferus. Sampling began on 13 September 2005, within 1 week after floodwater pumping was intitated, and continued through September 2006. More than 300 seafood, water, and sediment samples were analyzed for a suite of organic chemical contaminants, including organochlorines, polybrominated diphenyl ethers, and polycyclic aromatic compounds (PACs). The samples were also tested for bacterial contamination, including fecal contaminants such as Escherichia coli and potentially pathogenic Vibrio spp. While a range of both chemical and microbiological substances were detected, none were present in edible tissues at levels that posed any appreciable risk to human consumers of seafood products from the GoM, assuming that normal seafood preparation practices were followed. Petroleum-derived PACs in whites shrimp from both Lake Borgne and Mississippi Sound increased over several sampling periods in the fall and early winter (p < 0.001). However, these levels were quite low and had declined considerably by April 2006. Other than the increases in petroleum-derived PACs. our findings suggested little evidence of increased levels of contaminants immediately following the hurricane; however, the lackk of prestorm data hampered that determination. A lack of standard protocols, as well as issues related to risk assessment methodologies, complicated the ability to provide a coordinated multiagency communication of the results. As a result of our experiences in responding to this unprecedented environmental emergency. we recommend a more unified national capability for assessing seafood safety in our nation's coastal waters.