Influenza A (H5N1) is endemic in poultry across much of Southeast Asia, but limited information exists on the distinctive features of the few human cases. In Thailand, we instituted nationwide surveillance and tested respiratory specimens by polymerase chain reaction and viral isolation. From January 1 to March 31, 2004, we reviewed 610 reports and identified 12 confirmed and 21 suspected cases. All 12 confirmed case-patients resided in villages that experienced abnormal chicken deaths, 9 lived in households whose backyard chickens died, and 8 reported direct contact with dead chickens. Seven were children <14 years of age. Fever preceded dyspnea by a median of 5 days, and lymphopenia significantly predicted acute respiratory distress syndrome development and death. Among hundreds of thousands of potential human cases of influenza A (H5N1) in Asia, a history of direct contact with sick poultry, young age, pneumonia and lymphopenia, and progression to acute respiratory distress syndrome should prompt specific laboratory testing for H5 influenza.