Apalachicola Bay, Florida, is a highly productive and relatively pristine estuarine system. The Moderate-Resolution Imaging Spectroradiometer (MODIS) 250 m bands (1 & 2) have been shown to be effective in detecting and mapping water quality in bays and estuaries. This research examined the relationships between MODIS reflectance and chlorophyll-a and total suspended solids (TSS) concentrations in the Bay based on field data collected during October 14-17, 2002 and April 3-5, 2006, which were assumed to represent the physical and biological conditions in dry and wet seasons in terms of freshwater discharge into the Bay. We found that the best models for chlorophyll-a and TSS in October 2002 were the linear relationships between logarithmically transformed chlorophyll-a, TSS, and the ratio of Band 2: Band 1 (logarithmically transformed). The best model for chlorophyll-a in April 2006 was the exponential relationship between chlorophyll-a and the reflectance in Band 1, whereas the best model for TSS was the exponential relationship between logarithmically transformed TSS and the ratio of Band 2: Band 1 (logarithmically transformed). The maps of chlorophyll-a and TSS distributions derived from the best models revealed large spatial and temporal variations in chlorophyll-a and TSS across the entire Apalachicola Bay.