Estimates of chronic disease prevalence are needed to improve our understanding of marine disease epizootiology, which is poorly known for marine megafauna such as marine turtles. An emerging worldwide threat to green sea turtles (Chelonia mydas) is fibropapillomatosis (FP), which is a pandemic tumor-forming disease associated with herpesviruses. We report on a 26-yr FP epidemic in the Hawaiian Archipelago and show that apparent disease prevalence in the world's main endemic hot spot increased rapidly following a late 1980s outbreak, peaked during the mid-1990s, and then declined steadily ever since. While this disease is a major cause of sea turtle stranding in Hawaiian waters and can be fatal, we also show that long-term tumor regression can occur even for turtles with advanced FP. The endemic Hawaiian green turtle stock was severely depleted by overexploitation prior to protection under the US Endangered Species Act in 1978. This stock has increased significantly ever since, despite exposure to a major chronic disease epidemic that is currently declining.