The incidence of human rabies in the United States has decreased significantly over the past century. This analysis examines the ecological status of rabies in Louisiana with the intent of identifying differences in risk of rabies transmission from exposures to different species of animals. Louisiana presently harbors one terrestrial variant of rabies, a skunk variant, and several bat variants. Surveillance data collected from 1988 through 2007 were examined, comparing areas of the state characterized by circulating terrestrial variants and areas free of terrestrial rabies. Nine state public health regions were also compared. The proportions of rabies-positive laboratory submissions from each species and/or species group were used as indicators of risk. In addition, differences in proportions positive were examined temporally. A significant proportion of positive bats (9.64%) and skunks (44.3%), examined after biting or otherwise exposing a human being, were identified by diagnostic laboratories. Samples from wild terrestrial animals originating in areas known to harbor circulating terrestrial rabies variants were more than 30 times more likely to be positive for rabies than samples originating from areas thought to be free of terrestrial rabies. Bats were also slightly more likely to be positive when submitted from areas known to be endemic for terrestrial rabies. Rabies in pets and agricultural animals were rarely reported. Seasonal variations in prevalence of positive tests were also identified. The results of this examination of rabies epidemiology in Louisiana can be used in determining recommendations for both pre- and postexposure rabies prophylaxis. Similar applications of surveillance data are encouraged in other jurisdictions.