Early diagnosis of influenza infection is needed to optimize the benefit of prescribing antiviral drugs. However, the accuracy of rapid tests is highly variable. This study evaluated the performance of Directigen flu A+B enzyme immunoassay (EIA) and direct fluorescent assay (DFA) during the 2004-2005 influenza season. Participants with medically attended acute respiratory illness were identified through an active surveillance. Consenting patients (n=818) were enrolled and cultured for influenza. Physicians ordered a rapid antigen test (EIA or DFA) according to their clinical judgment. Physicians ordered rapid tests with EIA (n=109), DFA (n=86), or both (n=9) in 204 patients with acute respiratory illness who were also cultured for influenza. The EIA detected 18 of 43 influenza infections (sensitivity, 42%; 95% confidence interval [CI], 28-57%), whereas DFA detected 26 of 38 influenza infections (sensitivity, 68%; 95% CI, 53-81%). Compared with culture, specificity of both EIA and DFA was 96%. During the 2004-2005 influenza season, both the EIA and DFA had low sensitivity and failed to detect influenza in many patients.