CONTEXT: Overuse of antibiotics has contributed to microbial resistance, compromising the treatment of bacterial infections. Very high levels (>50%) of antibiotic resistance among invasive Streptococcus pneumoniae have been documented in Knox County, Tennessee. OBJECTIVE: To determine the effectiveness of a community-wide intervention aimed at reducing inappropriate antibiotic use among children. DESIGN, SETTING, AND PARTICIPANTS: The Knox County Health Department led a multifaceted year-long campaign (May 1997 through April 1998) aimed at decreasing unnecessary antibiotic use among children. Tennessee's 3 other major urban counties (Shelby, Hamilton, and Davidson) did not conduct similar campaigns and served as controls. Evaluation included white and black children (aged <15 years) enrolled in Tennessee's Medicaid Managed Care Program in the 4 study counties, representing 36% of the study counties' children (464 200 person-years observed). INTERVENTION: Educational efforts were directed toward health care practitioners (primarily via peer leader presentations) and to the parents of young children and the public (primarily via printed materials). MAIN OUTCOME MEASURE: The intervention-attributable effect on antibiotic use, defined as the excess percentage change in oral antibiotic prescription rates in Knox County between the 12-month preintervention and postintervention periods, relative to that of control counties. RESULTS: Antibiotic prescription rates declined 19% and 8% among Knox County and control county children, respectively, yielding an 11% intervention-attributable decline (95% confidence interval, 8%-14%; P<.001). The intervention-attributable decrease in prescription rates was greatest among children aged 1 to less than 5 years (among white children, 8% [P<.001]; among black children, 18% [P<.001]). CONCLUSIONS: A community-wide educational intervention reduced antibiotic prescription levels among children in Knox County.