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We have developed and illustrated a general regional multi-species model that describes the fate and transport of mercury in three forms, elemental, divalent, and methylated, in a generic regional environment including air, soil, vegetation, water, and sediment. The objectives of the model are to describe the fate of the three forms of mercury in the environment and to determine the dominant physical sinks that remove mercury from the system. Chemical transformations between the three groups of mercury species are modeled by assuming constant ratios of species concentrations in individual environmental media. We illustrate and evaluate the model with an application to describe the fate and transport of mercury in the San Francisco Bay Area of California. The model successfully rationalizes the identified sources with observed concentrations of total mercury and methyl mercury in the San Francisco Bay Estuary. The mass balance provided by the model indicates that continental and global background sources control mercury concentrations in the atmosphere but that loadings to water in the San Francisco Bay Estuary are dominated by runoff from the Central Valley catchment and remobilization of contaminated sediments deposited during past mining activities. The model suggests that the response time of mercury concentrations in the San Francisco Bay Estuary to changes in loadings is long, on the order of 50 years.