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A longitudinal epidemiologic study of cutaneous leishmaniasis (CL) transmission was conducted between July 1989 and June 1991 in a 1,200-km2 sector of the northeastern Sinai Desert monitored by the Multinational Force and Observers (MFO), an international peace keeping mission between Egypt and Israel. The occurrence of human cases, sand fly density, rodent collection, and isolations of Leishmania confirmed only one of four surveyed locations as a significant focus of CL transmission. Phlebotomus papatasi, the only anthropophilic sand fly species encountered at this focus, comprised more than 96% of the sand fly population and attained human landing densities exceeding 100 sand flies/person/hr during 1990. Seasonal activity of this species ranged from April to November, with highest densities occurring during the period May-September. A peak promastigote infection rate of 2.4% (13 of 534) was observed in P. papatasi during July 1990. Twelve of the 60 (20%) persons at risk during the six months of intense sand fly activity at this site developed lesions consistent with CL; L. major was isolated from nine (75%) of these cases. Leishmania major infection was acquired by two of 22 (9%) sentinel hamsters used during the same period. More than 97% of the 897 wild rodents trapped at this site were desert gerbil species. Leishmania major was the only Leishmania isolated from human, sand fly, wild rodent (Gerbillus pyramidum), and sentinel hamster infections that originated at site Check point 1-Delta, the focus of CL transmission within jurisdiction of the MFO. The altered ecology of this area, created by construction of a dam, may contribute significantly to the transmission dynamics of CL at this focus.