The quality of water flowing southward in the Everglades and Big Cypress Swamp was characterized by three synoptic surveys along an 80-mile section of the Tamiami Trail and along a 24-mile transect down the Shark River Slough, by monthly sampling of a background reference site in the central Big Cypress Swamp, and by sampling of fish tissue for contaminants at several sites near the Trail. The quality of water along the Trail is spatially variable due to natural and human influences. Concentrations of dissolved solids and common ions such as chloride and sulfate were lowest in the central and eastern Big Cypress Swamp and were higher to the west due to the effects of seawater, especially during the dry season, and to the east due to canal drainage from the northern Everglades. Concentrations of total phosphorus tended to decrease from west to east along the 80-mile section of the Trail, and were usually about 0.01 milligram per liter or less in the Everglades. Short-term loads (based on average discharge for 4 days) of total phosphorus and total Kjeldahl nitrogen (ammonia plus organic nitrogen) across four gaged sections of the Tamiami Trail were highest in the Everglades near the S-12 structures primarily due to the relatively greater discharges in that section. Concentrations of dissolved solids and total phosphorus at the central Big Cypress Swamp site increased significantly during the dry season as waters ponded. Effects of nearby, upstream agricultural activities were evident at a site in the western Big Cypress Swamp where relatively high concentrations of total phosphorus, total mercury, and dissolved organic carbon and high periphyton biomass accumulation rates were measured and where several pesticides were detected. The most frequently detected pesticides along the Trail were atrazine (14 detections), tebuthiuron (11 detections), and metolachlor (5 detections), and most concentrations were less than 0.1 microgram per liter. DDT compounds were the only pesticides detected in fish from five sites. Total DDT ranged from 5 to 6 micrograms per kilogram in largemouth bass and from 11 to 17 micrograms per kilogram in Florida gar.