We used monthly otter trawling and beach seining to sample the fishes of Suisun Marsh in the San Francisco Estuary from 1979 to 1999. We collected nearly 173,000 fish, mostly young of the year, representing 28 native species and 25 alien species. Catch data were related to temperature, salinity, water transparency, and several measures of freshwater inflow into the marsh. Species abundance and distribution within the marsh were the product of several interacting factors: (1) the timing and place of reproduction of the abundant resident species, (2) past reproductive success, (3) habitat differences among sloughs, and (4) physiological tolerance. We did not find consistent groups of potentially interacting species, although some native species showed weak concordance in abundance. The lack of persistent fish assemblages is related to the naturally fluctuating environmental conditions of the estuary, the overall decline in fish abundance through time, and the frequent invasions of alien fishes and invertebrates. Our results suggest that the fish assemblages in Suisun Marsh will continue to be unpredictable until estuarine processes approach their historic range of variability and alien invasions are halted.