Introduction: Mayotte, a French island in the Comoros archipelago in the Indian Ocean, is located in an area of high endemicity that includes the other islands of the archipelago, Madagascar, and East Africa. Since the last assessment of the leprosy situation on the island dates back to 1998, we felt it was important to conduct a new assessment, especially since the WHO had set a goal of eliminating leprosy worldwide by 2005. Results: The retrospective survey covering the years 1999 to 2005 shows that the disease remained endemic, with a prevalence of 4.47 per 10,000 as of December 31, 2005, and an annual detection rate that remained high (22 to 38 per 100,000 inhabitants). The characteristics of new cases were consistent with those found globally (predominance of males, adults under 45 years of age, and paucibacillary forms), with the exception, in the indigenous population, of a high percentage of patients under 15 years of age (29%) and more than one-third of familial cases. At the time of diagnosis, 7.8% of patients had a disability rating of 2. Conclusion: These findings underscore the need to strengthen efforts to combat the disease on this island. (R.A.)