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Recent advances in the diagnosis and treatment of influenza virus infections include: (1) rapid bedside diagnosis methods with simple commercially available tests; and (2) Food and Drug Administration approval of treatment for children 1 year of age and older with neuraminidase inhibitor drugs. For proven benefit antivirals should be used within 2 days of onset of symptoms.We conducted a performance improvement exercise comparing the sensitivity and specificity of four rapid tests for influenza viruses: (1) Flu OIA (Biostar); (2) Quickvue Influenza Test (Quidel); (3) Z Stat Flu (ZymeTx); and (4) Directigen Flu A (Becton Dickinson).During the 1999 to 2000 epidemic, symptomatic patients seen at the private practice of one of the authors provided specimens collected and processed according to the manufacturer’s directions. Throat swabs only were used to collect the specimens for the Z Stat Flu Kit. Directigen was performed immediately, and the others were run in parallel within 12 to 24 h. Specimens were frozen first at −20°C for up to 3 days and shipped in transport medium to the Virology Research Laboratory of the Virginia State Health Department for culture where they were stored at −60°C until cultured. Some of the samples were processed by a commercial laboratory.Specimens from 116 patients were available for influenza culture; for 88 of these culture was performed at the State Health Department Laboratory, and for 28 culture was performed at a local commercial medical laboratory. Influenza virus (A) was detected in 58 of 116 (50%) specimens, 10 (17%) of these only by direct fluorescent antigen samples. Viral culture-direct fluorescent antigen results were used as the standard. Of the 4 tests Biostar and Z Stat Flu required more technician time (by an average of 2-fold). The 4 tests had sensitivities ranging from 72 to 95%. Z Stat differed significantly in sensitivity from the other three (P = 0.001). The specificities of Directigen, Quickvue, Flu OIA and Z Stat Flu were similar (76 to 86%). The positive predictive value of Directigen, Quickvue and FluOIA and Z Stat ranged from 80 to 86%. The negative predictive value of all 4 tests ranged from 75 to 94%. Z Stat Flu had a lower negative predictive value than the other 3 tests (75%;P = 0.001.In this first head-to-head comparison of four rapid diagnostic tests for influenza, Directigen Flu A, Quickvue and Flu OIA appear equivalent in sensitivity, specificity, positive predictive value and negative predictive value. Z Stat Flu was not as sensitive or as efficient as the other three tests.