Clear Lake, California, USA, receives acid mine drainage and mercury (Hg) from the Sulphur Bank Mercury Mine, a U.S. Environmental Protection Agency (U.S. EPA) Superfund Site that was active intermittently from 1873 to 1957 and partially remediated in 1992. Mercury concentrations were analyzed primarily in four species of Clear Lake fishes: inland silversides (Menidia beryllina, planktivore), common carp (Cyprinus carpio, benthic scavenger/omnivore), channel catfish (Ictalurus punctatus, benthic omnivorous predator), and largemouth bass (Micropterus salmoides, piscivorous top predator). These data represent one of the largest fish Hg data sets for a single site, especially in California. Spatially, total Hg (TotHg) in silversides and bass declined with distance from the mine, indicating that the mine site represents a point source for Hg loading to Clear Lake. Temporally, fish Hg has not declined significantly over 12 years since mine site remediation. Mercury concentrations were variable throughout the study period, with no monotonic trends of increase or decrease, except those correlated with boom and bust cycles of an introduced fish, threadfin shad (Dorosoma petenense). However, stochastic events such as storms also influence juvenile largemouth bass Hg as evidenced during an acid mine drainage overflow event in 1995. Compared to other sites regionally and nationally, most fish in Clear Lake exhibit Hg concentrations similar to other Hg-contaminated sites, up to approximately 2.0 mg/kg wet mass (WM) TotHg in largemouth bass. However, even these elevated concentrations are less than would be anticipated from such high inorganic Hg loading to the lake. Mercury in some Clear Lake largemouth bass exceeded all human health fish consumption guidelines established over the past 25 years by the U.S. Food and Drug Administration (1.0 mg/kg WM), the National Academy of Sciences (0.5 mg/kg WM), and the U.S. EPA (0.3 mg/kg WM). Mercury in higher trophic level fishes exceeds ecotoxicological risk assessment estimates for concentrations that would be safe for wildlife, specifically the nonlisted Common Merganser and the recently delisted Bald Eagle. Fish populations of 11 out of 18 species surveyed exhibited a significant decrease in abundance with increasing proximity to the mine; this decrease is correlated with increasing water and sediment Hg. These trends may be related to Hg or other lake-wide gradients such as distribution of submerged aquatic vegetation.