No other lake as large as Lake Erie (surface area, 25,690 km²) has been subjected to such extensive changes in the drainage basin, the lake environment, and the fish populations over the last 150 years. Deforestation and prairie burning led to erosion of the watershed and siltation of valuable spawning grounds. Marsh spawning areas were drained. Lake-to-river spawning migrations of sturgeon, walleye, and other fishes were blocked by mill dams. Accelerated cultural nutrient loading increased total dissolved solids by nearly 50% (1920-70). Phosphate loading reached 469 metric tons per year by the 1950's and continued to increase. The biomass of phytoplankton increased 20-fold between 1919 and 1963. Oxygen demand for decomposition of these algae so degraded oxygen regimes in the western and central basins by the 1950's that the once abundant mayfly nymphs were destroyed and the central basin hypolimnion became anoxic. The sequence of disappearance or severe depletion of fish species was as follows: lake trout, sturgeon, lake herring, lake whitefish, sauger, blue pike, and walleye. Yellow perch are now declining. All resources were intensively exploited at one time or another. Lake trout suffered only this stress, but changes in the watershed significantly stressed sturgeon and lake whitefish. Degradation of the lake spawning grounds, benthos, and oxygen regimes culminated in severe stress by the 1950's on the remnants of the lake herring and lake whitefish, and on the sauger, blue pike, and walleye. Additional mortality may have been imposed on walleye and blue pike fry by predacious smelt that successfully colonized Lake Erie after first appearing in 1932. The cultural stresses, in the probable order of greatest to least net effects on the fish community of Lake Erie, appear to have been: (1) an intense, opportunistic, ineffectively controlled commercial fishery; (2) changes in the watershed, such as erosion and siltation of stream beds and inshore lake areas, and construction of dams in tributaries; (3) nutrient loading, destruction of biota, and reduction of dissolved oxygen; and (4) the competitive and predatory activities of invading species.