OBJECTIVES: Inappropriate use of antibiotics for treating infections of viral etiology has contributed to the growing public health problem of antibiotic resistance. Influenza has been shown to be a major cause of febrile illness for which antibiotics are inappropriately prescribed. The rate, pattern and cost of antibiotic prescribing for patients aged 5-49 diagnosed only with influenza in the ambulatory care setting have not been documented. METHODS: Combined data from the 1997-2000 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were used to estimate influenza visit and antibiotic prescribing rates. All visits with an exclusive diagnosis of influenza (ICD-9 487.X) were included. Visit costs were based on 2003 Medicare national average allowances and drug costs for a standard agent-specific course of treatment was calculated using average wholesale prices from 2003 Thompson MICROMEDEX Red Book. RESULTS: From 1997-2001, 6.6 million (95%CI: 5.6, 9.1) ambulatory care visits coded with a sole diagnosis of influenza were reported for children and adults 5-49 years; an average of 1.3 million annual visits. Sixty-seven percent of visits were made by adults 18-49 years at a rate of 6.9 visits/1000 persons annually (95%CI: 5.1, 8.7) compared to children 5-17 years at 8.5 visits/1000 persons annually (95%CI: 5.6, 11.3). Visits to office-based physicians, hospital emergency departments and outpatient departments accounted for 85%, 11% and 5% of visits, respectively. Antibiotics were prescribed at 2.5 million visits (38% of encounters) at an estimated cost of $93 million. Broad-spectrum antibiotics prescribed at 39% of visits where an antibiotic was prescribed accounted for $59 million of the total cost for antibiotics. Combined visit and antibiotic costs for the group totaled $441 million. CONCLUSIONS: Prescribing of antibiotics for influenza is widespread, increases medical costs and may contribute to antibiotic resistance. Increased use of vaccination and viral testing could reduce antibiotic use and result in cost savings.