Persons who have frequent contact with rodents as part of their occupation may be at increased risk of exposure to rodent-borne viruses such as Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome, and Whitewater Arroyo virus (WWA), a New World arenavirus. Eighty-one persons with possible occupational exposure to rodents completed questionnaires and provided specimens for serologic testing. Seventy-two participants reported handling rodents as part of their job. The mean total number of rodents handled during participants' careers was approximately 2200. IgG antibody to lymphocytic choriomeningitis virus was detected in serum from one (1.2%) participant. IgG antibody to SNV, WWA, and Amapari viruses was not detected in any of the serum specimens. Despite considerable exposure to rodents, participants did not have significant serological evidence of exposure to rodent-borne viruses.