In late 1999 and early 2000, an outbreak of hantavirus pulmonary syndrome (HPS) occurred in and around Los Santos, on the Azuero Peninsula of southwestern Panamá. This HPS episode, resulting in 22% case fatality, was linked to the Costa Rican pigmy rice rat, Oligoryzomys fulvescens costaricensis, which harbored a then undescribed hantavirus, Choclo virus. In addition, Cherrie's cane rat, Zygodontomys brevicauda cherriei, was identified as carrying a distinct hantavirus, Calabazo virus with no known pathogenicity to humans. Herein we present the ecological results of the outbreak investigations in the Azuero region. A total of 164 animals were captured, of which 126 were potential small, non-volant mammal hosts of a hantavirus: rodents in the family Muridae. There were significant differences in small mammal community structure between case sites and a negative control site. Differences were manifest in ecological measures of species diversity and in species evenness and heterogeneity measures, as indicated by Pairwise Euclidian distances and Morisita indices of community similarity. Our analyses suggest that human activities (i.e., deforestation for cattle ranching) coupled with environmental factors (i.e., increased precipitation) may have synergistically coalesced for an increased risk of HPS to area residents.