The efficacy and safety of orally administered clarithromycin and erythromycin in the treatment of community-acquired pneumonia were assessed in a multicenter, double-blind, randomized study. Two hundred sixty-eight patients were randomized to receive either clarithromycin, 250 mg twice a day, or erythromycin stearate, 500 mg 4 times a day, for 7 to 14 days. Efficacy was evaluable in 173 patients (92 for clarithromycin, 81 for erythromycin). No statistically significant difference in clinical success rate (cure or improvement) was observed between the two groups (clarithromycin, 97 percent; erythromycin, 96 percent). Both groups had identical radiologic response (97 percent with resolution or improvement). Similarly, no statistically significant difference in bacteriologic response toward the target pathogens was observed among evaluable patients (clarithromycin, 23/26; erythromycin, 17/17; p value = 0.287). Clinical response toward Mycoplasma and Chlamydia pneumonia was comparable between the two groups (clarithromycin, 15/16; erythromycin, 10/11). However, patients receiving erythromycin had a twofold higher incidence of adverse events, mostly related to the gastrointestinal system, and were five times more likely to withdraw from therapy because of drug-related adverse events. These results show that clarithromycin is as effective as erythromycin in the outpatient treatment of community-acquired pneumonia. Furthermore, the lower incidence of adverse events associated with clarithromycin indicates that it is more acceptable to patients and, therefore, can enhance compliance.