The 1918-21 influenza pandemic was the most lethal natural event in recent history. In the Pacific region, the pandemic´s effects varied greatly across different populations and settings. In this region, the pandemic´s lethal effects extended over 3 years, from November, 1918, in New Zealand to as late as July, 1921, in New Caledonia. Although a single virus strain probably affected all the islands, mortality varied from less than 0·1% in Tasmania, to 22% in Western Samoa. The varied expressions of the pandemic across the islands reflected the nature and timing of past influenza epidemics, degrees of social isolation, ethnicity and sex-related effects, and the likelihood of exposures to pathogenic respiratory bacteria during influenza illnesses. The high case-fatality rate associated with this pandemic seems unlikely to recur in future influenza pandemics; however, understanding the critical determinants of the mass mortality associated with the 1918-21 pandemic is essential to prepare for future pandemics.