To elucidate the early clinical characteristics of hantavirus pulmonary syndrome (HPS), we compared the clinical features of 24 cases of HPS with those of cases of bacteremic pneumococcal pneumonia (n = 30), influenza (n = 33), or unexplained adult respiratory distress syndrome (ARDS, n = 21). On admission, patients with HPS were less likely than outpatients with influenza to have reported sore throat (OR = 0.02, P < .01) and cough (OR = 0.1, P = .01) and were less likely than patients with pneumococcal pneumonia to have lobar infiltrates detected by chest roentgenography (OR = 0, P < .01). Multivariate discriminant analysis revealed that three clinical characteristics at admission (dizziness, nausea or vomiting, and absence of cough) and three initial laboratory abnormalities (low platelet count, low serum bicarbonate level, and elevated hematocrit level) served to identify all patients with HPS and to exclude HPS in at least 80% of patients with unexplained ARDS. These findings warrant further study and should facilitate the early recognition of patients with HPS, who may benefit from early critical-care intervention.