Community-acquired pneumonia is a frequent cause of hospitalization in the United States. For the organisms most frequently encountered, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and the atypical organisms, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella species, there fortunately are several treatment options available. Using decision analysis techniques, we conducted a cost-effectiveness analysis comparing intravenous monotherapy with either levofloxacin or azithromycin against the frequently used combination of cefuroxime plus erythromycin. When considering drug acquisition costs only, levofloxacin was the most expensive of the three regimens ($126 vs. $80 and $83 for azithromycin and ce-furoxime/erythromycin, respectively). When the costs of supplies and administration, adverse drug events, and treatment failures were included in the analysis, levofloxacin and azithromycin were found to be similar in cost per pneumonia cure ($208 vs. $228). Under all plausible scenarios, these newer agents, when used as monotherapy, were more cost-effective than the cefuroxime/erythromycin combination.