The impact of the toxic cyanobacterium Microcystis aeruginosa on estuarine food web production in San Francisco Estuary is unknown. It is hypothesized that Microcystis contributed to a recent decline in pelagic organisms directly through its toxicity or indirectly through its impact on the food web after 1999. In order to evaluate this hypothesis, phytoplankton, cyanobacteria, zooplankton, and fish were collected biweekly at stations throughout the estuary in 2005. Concentrations of the tumor-promoting Microcystis toxin, microcystin, were measured in water, plankton, zooplankton, and fish by a protein phosphatase inhibition assay, and fish health was assessed by histopathology. Microcystis abundance was elevated in the surface layer of the western and central delta and reached a maximum of 32 9 10 9 cells l -1 at Old River in August. Its distribution across the estuary was correlated with a suite of phytoplankton and cyanobacteria species in the surface layer and 1 m depth including Aphanizomenon spp., Aulacoseira granulata, Bacillaria paradoxa, Rhodomonas spp., and Cryptomonas spp. Shifts in the phytoplankton community composition coincided with a decrease in the percentage of diatom and green algal carbon and increase in the percentage of cryptophyte carbon at 1 m depth. Maximum calanoid and cyclopoid copepod carbon coincided with elevated Microcystis abundance, but it was accompanied by a low cladocera to calanoid copepod ratio. Total microcystins were present at all levels of the food web and the greater total microcystins concentration in striped bass than their prey suggested toxins accumulated at higher trophic levels. Histopathology of fish liver tissue suggested the health of two common fish in the estuary, striped bass (Morone saxatilis), and Mississippi silversides (Menidia audens), was impacted by tumor-promoting substances, particularly at stations where total microcystins concentration was elevated. This study suggests that even at low abundance, Microcystis may impact estuarine fishery production through toxic and food web impacts at multiple trophic levels.