For 35 months, we monitored hantavirus activity in rodent populations in central Arizona. The most frequently captured hantavirus antibody–positive rodents were Peromyscus boylii and P. truei. Antibody-positive P. boylii were more frequently male (84%), older, and heavier, and they survived longer on trapping web sites than antibody-negative mice. The number of antibody-positive P. boylii was greater during high population densities than during low densities, while antibody prevalence was greater during low population densities. Virus transmission and incidence rates, also related to population densities, varied by trapping site. The spatial distribution of antibody-positive P. boylii varied by population density and reflected the species preference for dense chaparral habitats. The focal ranges of antibody-positive P. boylii also demonstrated a patchy distribution of hantavirus.