A survey for phlebotomine sand flies (Diptera:Psycho- didae) in the Dominican Republic revealed that Lutzomyia cayennensis hispaniolae (Fairchild and Trapido) was widely distributed and fairly common. Lutzomyia christophei (Fairchild and Trapido) was more limited in geographic distribution. Specimens of the latter species were obtained by light traps, flight traps, and aspirator collection from human bait and resting sites. Laboratory colonies of both species were established and life-cycle data were obtained. Lutzomyia cayennensis females readily fed on Anolis lizards. Female Lu. christophei readily fed on rodents and were capable of experimentally transmitting a Dominican strain (Isabel-WR336) of Leishmania to BALB/c mice seven to ten days after biting infected mice. Development of the parasite occurred in the anterior midgut in both Lu. christophei and Lu. anthophora (Addis), a species that was also experimentally infected. The course of development in the sand fly was observed by dissecting 15 infected Lu. anthophora on days 1-7 post-feeding. Development in this species was parallel to that observed in the 17 Lu. christophei. Promastigotes from flies four and five days post-feeding were infective to hamsters, as determined by xenodiagnosis with sand flies and spleen culture. In culture medium, Leishmania-Isabel strain grew at a much slower rate than either of two strains of L. mexicana. Hamsters and TRC mice, experimentally inoculated from culture, showed no outward sign of infection until at least 2.5 months after inoculation with the Isabel strain. In the Dominican Republic, 10 of the 21 known case sites were visited. Coffee and cacao groves were characteristic of these sites. Two female Lu. christophei were captured while biting a patient. Four species of mammals (170 specimens) were trapped from five of the case sites and examined for leishmaniasis using various methods. None was found to be infected, though 4 of 44 Rattus rattus from one site were seropositive (1:16), as determined by indirect fluorescent antibody test. Lutzomyia christophei is most probably the vector of diffuse cutaneous leishmaniasis in the Dominican Republic. The identity of the reservoir remains unknown, but R. rattus is the most likely suspect.