Analysis of 6 yr of monthly water quality data was performed on three distinct zones of Florida Bay: the eastern bay, central bay, and western bay. Each zone was analyzed for trends at intra-annual (seasonal), interannual (oscillation), and long-term (monotonic) scales. the variables TON, TOC, temperature, and TN∶TP ratio had seasonal maxima in the summer rainy season; APA and Chla, indicators of the size and activity of the microplankton tended to have maxima in the fall. In contrast, NO3−, NO2−, NH4+, turbidity, and DOsat, were highest in the winter dry season. There were large changes in some of the water quality variables of Florida Bay over the study period. Salinity and TP concentrations declined baywide while turbidity increased dramatically. Salinity declined in the eastern, central, and western Florida Bay by 13.6‰, 11.6‰, and 5.6‰, respectively. Some of the decrease in the eastern bay could be accounted for by increased freshwater flows from the Everglades. In contrast to most other estuarine systems, increased runoff may have been partially responsible for the decrease in TP concentrations as input concentrations were 0.3–0.5 μM. Turbidity in the eastern bay increased twofold from 1991 to 1996, while in the central and western bays it increased by factors of 20 and 4, respectively. Chla concentrations were particularly dynamic and spatially heterogeneous. In the eastern bay, which makes up roughly half of the surface area of Florida Bay, Chla declined by 0.9 μg l−1 (63%). The hydrographically isolated central bay zone underwent a fivefold increase in phytoplankton biomass from 1989 to 1994, then rapidly declined to previous levels by 1996. In western Florida Bay there was a significant increase in Chla, yet median concentrations of Chla in the water column remained modest (∼2 μg l−1) by most estuarine standards. Only in the central bay did the DIN pool increase substantially (threefold to sixfold). Notably, these changes in turbidity and phytoplankton biomass occurred after the poorly-understood seagrass die-off in 1987. It is likely the death and decomposition of large amounts of seagrass biomass can at least partially explain some of the changes in water quality of Florida Bay, but the connections are temporally disjoint and the process indirect and not well understood.