Exploiting the high sensitivity of the chemiluminescence phenomenon, an accurate and sensitive point-ofcare test, called the ZstatFlu-II test (ZymeTx, Inc., Oklahoma City, Okla.), was developed to detect influenza virus infections. The ZstatFlu-II test takes 20 min and requires approximately 2 min of "hands-on" time for operational steps. The ZstatFlu-II test does not distinguish between infections with influenza virus types A and B. ZstatFlu-II test results are printed on Polaroid High-Speed Detector Film, allowing test results to be archived. A prototype version of the ZstatFlu-II test was evaluated during the 2000-to-2001 flu season with 300 nasal aspirate specimens from children at a pediatric hospital. Compared to culture, the ZstatFlu-II test had 88% sensitivity and 92% specificity. The Directigen test had a sensitivity of 75% and a specificity of 93%. The sensitivity of the ZstatFlu-II test was significantly higher than that of the Directigen test (P < 0.0574).The annual economic cost of influenza disease in the United States has been estimated at $3 billion to $5 billion (22). The Centers for Disease Control and Prevention reported in 2001 that influenza was associated with about 20,000 deaths nationwide and more than 100,000 hospitalizations (http://www.cdc .gov/ncidod/diseases/flu/fluinfo.htm). Worldwide estimates were considerably higher (16,17,24). Sensitive, specific, and rapid tests for influenza will greatly improve patient health care and reduce costs so that only "flu-positive" patients receive the recently approved antiviral treatments (9, 21). Rapid diagnostics for influenza will also prevent the misuse of antibiotics to "treat" the flu.Influenza disease is caused by influenza virus types A and B. Influenza virus types A and B are Orthomyxoviridae, characterized by the presence of an envelope penetrated by glycoprotein spikes with hemagglutinating and neuraminidase activities. Influenza virus also contains matrix protein, nucleoprotein, and three proteins with polymerase activity and a segmented negative-strand RNA genome (6, 19). These viruses are responsible for winter epidemics of respiratory illness in which the rates of infection are highest among children (5). The shared cardinal sign of fever without localization makes differentiation of influenza from sepsis necessary for proper patient management. Delay in this differentiation could result in unnecessary laboratory testing and treatment for possible bacterial "sepsis" with unnecessary antibiotics (25).Three diagnostic methods for respiratory secretions are in common use. Culture, both shell vial and tube, takes several days. Direct or indirect immunofluorescence assays on exfoliated nasal pharyngeal cells could be done in a few hours but require a high level of expertise (10). Finally, rapid, point-ofcare tests are available to detect the influenza virus (3,12,20,23). All of these tests use an enzyme immunoassay directed at antigens of the viruses (3, 12, 23), with the exception of the ZstatFlu test, which detects influenza virus neur...