The Binax NOW Flu A and Flu B (Binax NOW), direct fluorescent assay (DFA), and viral culture were evaluated and compared with a composite of viral culture or reverse transcription polymerase chain reaction (RT-PCR). Participants with medically attended acute respiratory illness were identified through active surveillance during the 2006 to 2007 season, and consenting individuals (n=932) were tested for influenza by culture and RT-PCR. Physicians ordered a rapid antigen test (Binax NOW [n=73] or DFA [n=70]) according to their clinical judgment. The Binax NOW detected 11 of 18 influenza infections (sensitivity, 61%; 95% confidence interval [CI], 36-83%), whereas DFA detected 17 of 21 influenza infections (sensitivity 81%, 95% CI, 58-95%). Compared with culture/RT-PCR, specificity of both Binax NOW and DFA was 100%. During the 2006 to 2007 influenza season, DFA and Binax NOW demonstrated high specificity but failed to identify a substantial proportion of influenza infections.