Walker Lake is a monomictic, nitrogen-limited, terminal lake located in western Nevada. It is one of only eight large (Area>100 km2, Zmean > 15 m) saline lakes of moderate salinity (3–20 g/L) worldwide, and one of the few to support an endemic trout fishery (Oncorhynchus clarki henshawi). As a result of anthropogenic desiccation, between 1882 and 1996 the lake’s volume has dropped from 11.1 to 2.7 km3 and salinity has increased from 2.6 to 12–13 g/L. This study, conducted between 1992 and 1998, examined the effects of desiccation on the limnology of the lake. Increases in salinity over the past two decades caused the extinction of two zooplankton species, Ceriodaphnia quadrangula and Acanthocyclops vernalis. Recent increases in salinity have not negatively affected the lake’s dominant phytoplankton species, the filamentous blue-green algae Nodularia spumigena. In 1994 high salinity levels (14–15 g/L) caused a decrease in tui chub minnow populations, the main source of food for Lahontan cutthroat trout, and a subsequent decrease in the health of stocked trout. Lake shrinkage has resulted in hypolimnetic anoxia and hypolimnetic accumulation of ammonia (800–2000 µg-N/L) and sulfide (15 mg /L) to levels toxic to trout. Internal loading of ammonia via hypolimnetic entrainment during summer wind mixing (170 Mg-N during a single event), vertical diffusion (225–500 Mg-N/yr), and fall destratification (540–740 Mg-N year-1) exceeds external nitrogen loading (<25 Mg-N/yr). Increasing salinity in combination with factors related to hypolimnetic anoxia have stressed trout populations and caused a decline in trout size and longevity. If desiccation continues unabated, the lake will be too saline (>15–16 g/L) to support trout and chub fisheries in 20 years, and in 50–60 years the lake will reach hydrologic equilibrium at a volume of 1.0 km3 and a salinity of 34 g/L.