Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis in the United States, typically is associated with the consumption of raw oysters gathered from warm-water estuaries. We describe a recognized outbreak of V. parahaemolyticus infection associated with the consumption of seafood from Alaska. After we received reports of the occurrence of gastroenteritis on a cruise ship, we conducted a retrospective cohort study among passengers, as well as active surveillance throughout Alaska to identify additional cases, and an environmental study to identify sources of V. parahaemolyticus and contributors to the outbreak. Of 189 passengers, 132 (70 percent) were interviewed; 22 of the interviewees (17 percent) met our case definition of gastroenteritis. In our multiple logistic-regression analysis, consumption of raw oysters was the only significant predictor of illness; the attack rate among people who consumed oysters was 29 percent. Active surveillance identified a total of 62 patients with gastroenteritis. V. parahaemolyticus serotype O6:K18 was isolated from the majority of patients tested and from environmental samples of oysters. Patterns on pulsed-field gel electrophoresis were highly related across clinical and oyster isolates. All oysters associated with the outbreak were harvested when mean daily water temperatures exceeded 15.0 degrees C (the theorized threshold for the risk of V. parahaemolyticus illness from the consumption of raw oysters). Since 1997, mean water temperatures in July and August at the implicated oyster farm increased 0.21 degrees C per year (P<0.001 by linear regression); 2004 was the only year during which mean daily temperatures in July and August at the shellfish farm did not drop below 15.0 degrees C. This investigation extends by 1000 km the northernmost documented source of oysters that caused illness due to V. parahaemolyticus. Rising temperatures of ocean water seem to have contributed to one of the largest known outbreaks of V. parahaemolyticus in the United States. Copyright 2005 Massachusetts Medical Society.