Hantavirus pulmonary syndrome (HPS) is a rare but acute fulminant disease caused by Sin Nombre virus (SNV). To understand the role of the viral load in the pathogenesis of HPS, the load of virus in the blood of patients with HPS was measured. A quantitative reverse transcription-polymerase chain reaction assay was developed for SNV, because SNV is difficult to grow in cell culture. Thirty-eight samples from 26 patients with HPS were analyzed. Twenty of the 26 initial samples were positive for viral RNA (7 of 9 samples were obtained from patients with fatal cases, and 13 of 17 were obtained from survivors). Mean viral RNA copy numbers were 106.1+/-1.4/mL in positive cases (106.7+/-1.4/mL in fatal cases, 105.8+/-1.3/mL in survivors) and were correlated with peak hematocrit (P<.05) and with the lowest platelet count (P=.05). In 8 survivors who had serial samples obtained, viral RNA copy numbers decreased promptly after resolution of fever.