The long-term objective of this research is understanding the epidemiology of leishmaniasis in the United States, including mechanism of transmission, geographic distribution, and interrelationships of hosts and vectors. Twenty-nine autochthonous cases of human cutaneous leishmaniasis caused by Leishmania mexicana are known from Texas. Population growth and changing demographic patterns could lead to an increase in human disease in the United States. There is the additional risk that more virulent species of Leishmania could be introduced into southern Texas, which is ecologically receptive to the parasite. Increased knowledge of the ecology of leishmaniasis in the United States is necessary if its emergence as a disease of increasing importance is to be prevented. It is hypothesized that Neotoma micropus is the principal reservoir of L. mexicana in Texas, and that opossums (Didelphis virginiana), nine-banded armadillos (Dasypus novemcinctus), hispid cotton rats (Sigmodon hispidus), white-footed mice (Peromyscus Ieucopus), Mexican ground squirrels (Spermophilus mexicanus), rock squirrels (Spermophilus variegatus) and species of canidae and felidae (wild and domestic) are secondary hosts, with prevalences < 20%. These species will be collected within the city of San Antonio and screened for L. mexicana by culture and the Polymerase Chain Reaction (PCR). Sand flies (Lutzomyia spp) will be collected from localities where mammals are trapped and screened for Leishmania through culture and PCR. A second hypothesis, that enzootic foci of L. mexicana exist north and west of the known foci in southern Texas, will be tested by conducting studies in central and western Texas, and Arizona. Woodrats, rock squirrels and sand flies from Leander, Texas; Big Bend National Park, Texas; and Buenos Aires National Wildlife Refuge, Arizona will be collected and screened for Leishmania.