Rodents are the principal hosts of Sin Nombre virus, 4 other hantaviruses known to cause hantavirus pulmonary syndrome in North America, and the 3 North American arenaviruses. Serum samples from 757 persons who had worked with rodents in North America and handled neotomine or sigmodontine rodents were tested for antibodies against Sin Nombre virus, Whitewater Arroyo virus, Guanarito virus, and lymphocytic choriomeningitis virus. Antibodies against Sin Nombre virus were found in 4 persons, against Whitewater Arroyo virus or Guanarito virus in 2 persons, and against lymphocytic choriomeningitis virus in none. These results suggest that risk for infection with hantaviruses or arenaviruses usually is low in persons whose occupations entail close physical contact with neotomine or sigmodontine rodents in North America.