Upper respiratory tract infections (URTIs) are among the most common diseases in children, and they can be very distressing not only for the sick child and his or her parents but also for the physician. The burden of these URTIs is reflected by: (1) high incidence; (2) substantial morbidity and potential sequelae; (3) tendency to overdiagnosis (especially in streptococcal pharyngitis and acute otitis media); (4) associated overuse and misuse of antibiotics. Many URTIs are viral in etiology, and many bacterial URTIs are self-limiting. Unnecessary antibiotic therapy (overuse) and poor therapeutic choice, dosage and/or duration (misuse) both contribute to bacterial resistance, avoidable toxicity and increased costs. OPTIMUM APPROACH A key issue in modern antibacterial thinking is the relationship among body systems, antibiotics and causative pathogens. In particular the pharmacokinetics and pharmacodynamics of an antibiotic are central to its efficacy for a given indication. The ideal therapy for URTIs must combine excellent clinical efficacy with a high rate of bacteriologic eradication. To achieve this an antibiotic requires outstanding antibacterial potency and must be able to act in synergy with host defenses. In addition a good tolerability profile and a simple dosing regimen are vital to maximize patient compliance. Azithromycin, an azalide antibiotic, fulfills these criteria, which explains its established role for treatment of numerous infectious diseases including URTIs. TREATMENT STUDIES Current expert and advisory committees agree that clinical trials in URTIs must adhere to the best science, be acceptable to patients and parents and be feasible for sponsors. Adherence to best possible science takes into account the often self-limiting course of URTIs on the one side and balances that with possible complications and sequelae on the other. This approach also takes into account available efficacy and safety data and recognizes the gaps in these data. Science also must acknowledge that children should not be included in certain experimental study designs. Acceptability to patients and parents requires that trials are ethically justifiable. As such, particularly invasive procedures such as tympanocentesis need a clear indication. Moreover drug characteristics supporting patient compliance merit priority, e.g. simple dosage regimen, good tolerability and agreeable palatability. Feasibility for sponsors demands logistically doable trials without unnecessarily restrictive governing criteria. Industry certainly weighs research effort vs. profit differently for acute and chronic therapies. In addition competition for the small number of suitable study centers should be avoided. PURPOSE OF SUPPLEMENT On July 21, 2003 a small panel of experts met for a closed symposium to discuss and review the key azithromycin studies for treatment of pediatric URTIs. The major aim of this meeting was to publish proceedings that address the role of azithromycin in URTIs in an everyday clinical context, i.e. with a focus on the clinical relevance to patients and their parents. In particular the rationale for single dose and high dose treatment regimens with azithromycin were discussed, and the available studies with these novel regimens in acute otitis media and streptococcal pharyngitis were reviewed. Emphasis was placed on study design (science, acceptability, feasibility), clinical efficacy and bacteriologic eradication, bacterial resistance issues, safety, tolerability and compliance.