This study evaluates factors, particularly water quality related, that may influence mercury (Hg) bioaccumulation in largemouth bass (LMB, Micropterus salmoides Lacépède) within the Everglades marshes of South Florida. The investigation is an empirical analysis of ambient data from both long-term fish monitoring and marsh water quality monitoring sites across the Everglades Protection Area. Previous Hg studies of Everglade's marsh biota have focused on the role that sulfate plays in Hg bioaccumulation. While sulfate can be important under some environmental conditions, this empirical analysis in Everglades marshes showed that sulfate has little association with Hg concentrations in LMB. It is suggested that other water quality variables including water pH, alkalinity and specific conductance may have as much or more influence in the accumulation of Hg in LMB. Furthermore, tissue Hg concentration normalized to body-weight and age-specific growth rates were significantly correlated with Water Conservation Area (WCA)-1, WCA-2 and Everglades National Park (ENP) but not WCA-3. However, body condition was correlated negatively with Hg concentration only within WCA-2, WCA-3 and ENP; the relationship was not significant within WCA-1. This disparity between Hg concentration and body condition could be attributed to ecological effects including water quality and quantity conditions within each compartment of the system that are significant driving forces for biota abundance, trophic structure and distribution within the Everglades ecosystem. While water quality and quantity are important, trophic position of LMB has the potential to influence Hg accumulation dynamics. In spite of documented biogeochemical linkages to Hg accumulation, this empirical analysis did not demonstrate enough quantitative interaction to be useful for Hg management in the Everglades ecosystem.