To determine if individuals with extensive exposure to rodent habitats were infected with Sin Nombre hantavirus (SNV), we evaluated forest and park service personnel from the region of endemicity in the southwestern United States. Information about work and recreational activities, including exposure to rodents and a history of recent illnesses, was obtained via a standardized questionnaire. Serum specimens were also collected. Of 140 participating workers, 84 (60%) were primarily engaged in outdoor work activities, 14 (10%) were office-based supervisors, and 42 (30%) were office workers. Of the 140 employees, 89 (64%) reported repeated exposures to rodents, rodent nests, and/or rodent droppings; 22 (16%) reported trapping or handling wild rodents. Hantavirus antibodies were not detected in any park employee. These data suggest that transmission of SNV is a rare event even among persons in the southwestern United States who have a high level of exposure to this virus. Although park employees and visitors in this region are at low risk of infection with SNV, these persons should continue to use recommended measures for risk reduction.