Background: In October 1995, the island’s sole physician reported approximately 50 cases of acute appendicitis among the population of Île de la Désirade (1,605 residents) to the DDASS. We present the full scope of the investigations conducted to describe this phenomenon and generate hypotheses regarding its origin. Methods: A comprehensive search for cases of appendectomies performed between August 10, 1995, and July 22, 1996, within the population was conducted. We reviewed all available hospitalization records, examined the appendectomy slides, interviewed the patients and their families to reconstruct individual and family medical histories, assessed the prevalence of infectious and parasitic carriers within the population, and analyzed the quality of the water in the distribution network. Results: Two hundred twenty-six cases of appendectomies were identified (14.1% of the island’s population); 40% occurred during the May–June 1996 period; 46% were in men and 40% in children under 15 years of age. Clinical, laboratory, and pathological data do not support the existence of an epidemic of acute appendicitis or acute appendicular syndromes. Epidemiological investigations conducted among the cases and their families do not suggest a phenomenon of mass food poisoning or human-to-human transmission. However, they reveal the frequent occurrence of nonspecific abdominal pain, of a subacute or chronic nature. Stool tests conducted in the population show no parasitic infestation or abnormally frequent bacterial contamination. The results of the health inspection of the drinking water supply comply with regulations, and the specific analyses performed show no chemical contamination of the water. Conclusions: The investigations conducted did not identify a single infectious or toxic cause responsible for the high prevalence of chronic abdominal disorders within an isolated population. In this island setting, an inappropriate medical and surgical response was likely the cause of this epidemic of appendectomies, which had significant public health consequences. (R.A.)