BACKGROUND AND PURPOSE The clinical manifestations of severe acute respiratory syndrome (SARS) and mycoplasma pneumonia are similar. However, administration of corticosteroid to Mycoplasma pneumoniae patients suspected of having SARS may unnecessarily increase the risk of opportunistic infection. We compared the clinical course of 13 SARS patients and 6 patients with mycoplasma pneumonia treated during the outbreak of SARS in Taiwan. METHODS Patients admitted due to suspicion of SARS with a subsequent diagnosis of SARS or Mycoplasma pneumoniae pneumonia were included. RESULTS The initial clinical manifestations were similar in patients with SARS and those with M. pneumoniae infection. However, SARS patients had more severe lymphopenia (p = 0.013) and anemia (p = 0.007), and more persistent pulmonary infiltrates (p = 0.023). Respiratory failure developed in 15.4% of the SARS patients and in none of the M. pneumoniae patients. Recovery from thrombocytopenia was associated with defervescence in 12 SARS patients and radiographic improvement in 6 in the following 5 days. In those with unsatisfactory resolution of the pulmonary infiltrates, corticosteroid therapy was associated with rapid radiographic improvement. CONCLUSIONS Because of similar initial presentations, differentiating SARS from M. pneumoniae pneumonia is very difficult based on symptomatology. In this series, lymphopenia and anemia were more severe in SARS than in M. pneumoniae infection, and SARS patients had more persistent and more new pulmonary infiltrates after hospitalization.