Rotuma is an isolated Polynesian island. In January 1911, most residents of Rotuma (population approximately 2,600) were exposed to measles virus for the first time. The official mortality register documented 491 deaths due to all causes among Rotumans during 1911 (cumulative measles-related mortality: 12.8%); most deaths occurred in April?May and were attributed to measles and its sequelae. Measles-related mortality rates were higher among young children (23.4 per 100 person-years) and young adults (17.1 per 100 person-years) than among adolescents (11.0 per 100 person-years) and older adults (5.6 per 100 person-years); females (16.2 per 100 person-years) died at a higher rate than males (13.2 per 100 person-years). Gastrointestinal complications (75%), not respiratory complications, were the predominant clinical manifestations of fatal measles cases; tuberculosis mortality was unusually high during the year of the epidemic. In 1911, measles-related mortality varied by nearly 3-fold across geographic districts (range, 7.4%?21.6%). The extreme mortality due to measles on Rotuma typifies the experiences of isolated populations after first encounters with measles; it suggests that prior exposures to a narrow range of microbes and genetic homogeneity predispose isolated populations to lethal outcomes when they are first exposed to highly contagious and pathogenic viruses (e.g., measles, influenza).