Hantavirus pulmonary syndrome (HPS) is an acute respiratory illness with high mortality. It is caused by a newly described New World hantavirus known as Four Corners virus (FCV). Nearly all cases of HPS have occurred in the western United States. The etiologic agents in those cases have been closely related to each other, based upon comparisons of their genetic sequences. We have molecularly cloned the S genomic segment of a hantavirus (Rl-1) implicated in a case on HPS in the northeastern United States. Nucleotide sequence analysis shows that the Rl-1 virus has many similarities to FCV, but is clearly distinct from the western forms of that virus. These data suggest that HPS can be caused by multiple agents that together form a distinctive evolutionary clade.