Sin Nombre virus (SNV) causes the zoonotic disease hantavirus pulmonary syndrome (HPS). Its mechanisms of transmission from rodent to human are poorly understood. It is possible that specific genetic signature sequences could be used to determine the probable site of each case-patient's exposure. Environmental assessments suggested 12 possible sites of rodent exposure for 6 HPS patients. Rodents were captured at 11 of the 12 sites and screened for SNV infection within 2 weeks of the patient's diagnosis. Viral sequences amplified from tissues of rodents at each site were compared with those from case-patients' tissues. Rodents bearing viruses with genetic sequence identity to case-patients' viruses across 2 genomic segments were identified in 4 investigations but never at >1 site. Indoor exposures to rodents were especially common at implicated sites. By distinguishing among multiple possible sites of exposure, viral genotyping studies can enhance understanding of the conditions associated with infection by SNV.