Human alterations of the hydrologic regime during the past century have threatened the integrity of the subtropical Everglades. The monumental government-sponsored effort that is currently underway to restore the structure and function of this ecosystem has the rebirth of reasonably natural water flows as a major focus. However, this wet season-dry season system also is hostage to natural rainfall events and frequent tropical cyclones, which periodically cause severe flooding. This study examined the effect of severe high water levels, resulting from above normal summer rainfall and a fall tropical storm in 1994–1995, on white-tailed deer (Odocoileus virginianus seminolus), an important prey base for the endangered Florida panther (Puma concolor coryi) and other endemic carnivores. Flood waters at depths exceeding 60 cm, the generally accepted depth at which deer mobility is compromised, existed from November 1994 through the early half of 1995. Of 51 radiocollared deer alive at the onset of the flood on 1 November 1994, 25 (50%) died prior to 31 March 1995. The annual death rate of adult deer during the flood year was approximately double that of pre-flood years. Fawn production in 1995 appeared to be reduced approximately 10-fold from that in 1994, the pre-flood year. High water levels restricted use by deer of wet prairie habitat (87%), characterized by higher quality forage, and forced them to the slightly elevated tree islands (7%), characterized by lower quality forage. These findings demonstrate that severe high water events are detrimental to growth and maintenance of white-tailed populations in the Everglades. As a management safeguard, it is recommended that the water-depth levels considered to influence deer populations negatively in the Everglades system be lowered to 50 cm from the previously published level of about 60 cm. Strategies to restore functional hydrologic regimes to enhance floral and faunal benefits in the Everglades also must include consideration of the effects of natural weather events.