Azithromycin is an azalide antibiotic with activity against many of the respiratory pathogens and with marked tissue affinity. In a prospective study, the efficacy of a short-course of azithromycin was evaluated in 25 patients with community-acquired pneumococcal pneumonia. Gram-positive diplococci were abundant in the sputum smears of all patients, and Streptococcus pneumoniae was isolated in the sputum cultures of 15; one patient had pneumococcal bacteremia, as well. Azithromycin was administered at a single dose of 1,000 mg on day 1, and 500 mg on subsequent days for a total of three days in 19 patients, five days in four patients, two and four days in one patient each. Defervescence occurred within 24 hours after the first dose. The overall clinical cure and bacteriologic eradication rates were 96% and 93%, respectively. One patient with pneumococcal bacteremia failed to respond and died in respiratory failure. Side-effects were encountered in three (12%) patients. In conclusion, three-day therapy with a total azithromycin dose of 1,500 mg seems effective and safe in patients with community-acquired pneumococcal pneumonia and no underlying pulmonary condition.