In September 2000 an outbreak of influenza-like illness was reported on a cruise ship sailing between Sydney and Noumea with over 1,100 passengers and 400 crew on board. Laboratory testing of passengers and crew indicated that both influenza A and B had been circulating on the ship. The cruise coincided with the peak influenza period in Sydney. Morbidity was high with 40 passengers hospitalized, two of whom died. A questionnaire was sent to passengers 3 weeks after the cruise and 836 of 1,119 (75%) responded. A total of 310 passengers (37%) reported suffering from an influenza-like illness (defined as cough, fever, myalgia and weakness) and 528 (63%) had seen a doctor for illness related to the cruise. One-third of passengers reported receipt of influenza vaccination in 2000; however neither their rates of influenza-like illness nor hospitalization were significantly different from those in unvaccinated passengers. A case-control study also found no significant protective effect of influenza vaccination. With the increasing popularity of cruise vacations, such outbreaks are likely to affect increasing numbers of people. Whilst influenza vaccination of passengers and crew may afford some protection, uptake and effectiveness may not be sufficient to prevent outbreaks. Surveillance systems and early intervention measures, such as antiviral therapies, should be considered to detect and control such outbreaks.