As the incidence of dengue increases globally, US travelers to endemic areas may be at an increased risk of travel-associated dengue. Data from the US Centers for Disease Control and Prevention's laboratory-based Passive Dengue Surveillance System (PDSS) were used to describe trends in travel-associated dengue reported from January 1, 1996 to December 31, 2005. The PDSS relies on provider-initiated requests for diagnostic testing of serum samples via state health departments. A case of travel-associated dengue was defined as a laboratory-positive dengue infection in a resident of the 50 US states and the District of Columbia who had been in a dengue-endemic area within 14 days before symptom onset. Dengue infection was confirmed by serologic and virologic techniques. One thousand one hundred and ninety-six suspected travel-associated dengue cases were reported-334 (28%) were laboratory-positive, 597 (50%) were laboratory-negative, and 265 (22%) were laboratory-indeterminate. The incidence of laboratory-positive cases varied from 1996 to 2005, but had an overall increase with no significant trend (53.5 to 121.3 per 10(8) US travelers, p = 0.36). The most commonly visited regions were the Caribbean, Mexico and Central America, and Asia. The median age of laboratory-positive cases was 37 years (range: <1 to 75 y) and 166 (50%) were male. Of the 334 laboratory-positive cases, 41 (12%) were hospitalized, and 2 (1%) died. Residents of the US traveling to dengue-endemic regions are at risk of dengue infection and need to be instructed on appropriate prevention measures prior to travel. Especially in light of the potential transmissibility of dengue virus via blood transfusion, consistent reporting of travel-associated dengue infections is essential.