One hundred and sixty black South African gold miners with acute pneumococcal pneumonia were enrolled in a prospective randomized double-blind trial comparing roxithromycin (150 mg 2 X day) with cephradine (1.0 g 2 X day). Ninety patients with pneumonia caused by Streptococcus pneumoniae were treated for 5-10 days. Forty-three of 46 (93.4%) of the roxithromycin and all 44 (100%) of the cephradine treated groups had satisfactory clinical responses. In eight of the 46 (17%) roxithromycin treated patients and 10 of the 44 (23%) cephradine treated patients, Streptococcus pneumoniae was not eradicated from sputum cultures by the tenth day. Side effects in 18 patients (20%) were mild and were usually manifested by elevation of the transaminases; these were more common in the cephradine group (12) than in the roxithromycin group (5). Roxithromycin appears to be a safe and effective oral antibiotic for treatment of patients with mild to moderate pneumococcal pneumonia.