BACKGROUND: Numerous new oral antibiotics have been produced over the last few years with the aims of improving treatment for lower respiratory tract infections. AIM: The aim of the study was to compare the efficacy of an established drug, amoxycillin, with a new macrolide, clarithromycin, for initial treatment of adults with community-acquired lower respiratory tract infection. METHOD: Consecutive adults fulfilling a standard definition of lower respiratory tract infection presenting to 14 general practitioners in two neighbouring practices were allocated to antibiotic therapy in a random, single-blind manner. The outcome of treatment was assessed by the time taken by the patient to return to normal activities or work, the speed of resolution of symptoms, number of repeat consultations and side effects. RESULTS: The profile of the 221 patients receiving amoxycillin was very similar to that of the 221 receiving clarithromycin. The two groups did not differ greatly in requirement to visit the general practitioner again within either 4 weeks (20% amoxycillin group; 25% clarithromycin group) or 3 months (31% compared with 36%) of the original infection, in time taken to return to normal activities (6 days for group taking amoxycillin; 5 days for those on clarithromycin) or work (5 days for both groups), or in speed of resolution of symptoms. Compliance was good and the side-effects reported were similar for both groups. No increase in gastrointestinal complaints was noted for patients taking the macrolide. CONCLUSION: Amoxycillin and clarithromycin appear to be equally effective as initial therapy and to be tolerated in similar ways. Use of the newer drug appears to have no advantages over use of the accepted standard treatment.