BACKGROUND: There is good evidence of reduced prescribing of antibiotics in recent years, but the reason for this has not been established. AIM: To study the incidence of respiratory tract infections presenting to general practitioners (GPs) in England and Wales in relation to the incidence of other infections and to the prescription of antibiotics. SETTING: Sentinel practices in England and Wales who contribute to the Weekly Returns Service (WRS) of the Royal College of General Practitioners. DESIGN: Time-series analysis of disease incidence data reported by the practices and of antibiotic prescription data from the Prescription Pricing Authority (PPA) during the years 1994-2000. METHOD: Incidence data reported weekly from 73 practices in England and Wales, serving a population of 600,000, for acute respiratory tract infections, otitis media, infectious mononucleosis, shingles, urinary tract infections, and skin infections, were consolidated into quarterly datasets and examined graphically for evidence of secular and seasonal trends. Trends in antibiotic prescription items (data for England only were supplied by the PPA) were examined for association after adjustment for seasonal variation. RESULTS: The incidence of respiratory tract infections and antibiotic prescribing showed virtually identical seasonal variation, with both declining from 1995: respiratory tract infections by 48% in winter and 38% in summer, and antibiotic prescriptions by 34% and 21%, respectively. Trends in both were very highly correlated. The incidence of shingles and skin infections was constant. The incidence of urinary tract infections declined by 10%. The incidence of otitis media in children and acute bronchitis in the elderly followed the all-age trend in the reduction of respiratory tract infections. CONCLUSION: The considerable reduction in the incidence of respiratory tract infections between 1995 and 2000 is the main reason for the decline in antibiotic prescribing rather than changing prescribing thresholds for antibiotics.