This study compared the efficacy and tolerability of once-daily dosing with either roxithromycin or cefixime in previously healthy adult patients aged between 18 and 60 with markers of uncomplicated community-acquired pneumonia (CAP) in three outpatient clinics in an open, randomized study. Sixty patients were enrolled: 17 males and 13 females received roxithromycin 300 mg once daily for 8-10 days and 22 males and eight females received 400 mg cefixime once daily for the same period. All patients were assessed clinically, radiologically and bacteriologically before inclusion, immediately after the study and approximately 1 month later. The most common pathogen isolated from sputum was Streptococcus pneumoniae (in 26 (43%) of 60 patients), with mixed organisms isolated from the sputum of 18 (30%) of 60 patients. Staphylococcus aureus, Haemophilus influenzae or Moraxella catarrhalis occurred in 11/60 patients, and atypical pathogens were detected by serology in 7/26 cases in the roxithromycin group and 3/23 in the cefixime group. The severity of infection was rated as mild to moderate at the beginning of the trial. At the end of the study treatment period, clinical cure rates were 30/30 (100%) for roxithromycin and 28/30 (94%) for cefixime, with one patient on cefixime being classed as a partial responder and one patient being classed as a failure and withdrawn. However, radiological abnormalities persisted in three patients on roxithromycin and one on cefixime. Of the 59 patients who completed the study, none required further antibiotic therapy. No abnormal laboratory parameters or adverse events were reported in either group. Roxithromycin at a daily dose of 300 mg was an effective and well-tolerated treatment for the empirical treatment of mild to moderate CAP in this group of patients.