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Leishmania major strains cause human cutaneous leishmaniasis in Various arid regions in the Old World. Nevertheless, there is apparently no anthroponotic transmission even when the incidence of cases is very high and the involvement of reservoir animals is obligatory. To investigate this phenomenon we compared the development of L. major in Phlebotomus papatasi artificially infected with parasites in human, rabbit, or sand rat blood. The parasites, sandflies, and reservoir rodents came originally from the Jordan Valley. Following meals of promastigotes in human blood, parasites were retained in 48.0% and heavy infections developed in 6.6% of the sandflies. Such meals with sand rat blood resulted in 76.9% infected, including 58.5% heavily infected flies, whereas rabbit blood produced intermediate results. Similar results were obtained when infections were initiated with amastigotes and the infection rates were significantly different. Only flies with heavy infections are considered as potential transmitters of leishmaniasis. The adverse effect of human blood was attributed to the erythrocytes after similar experiments in which sandflies ingested promastigotes either with human erythrocytes and rabbit plasma or rabbit erthrocytes and human plasma. Amastigotes of an Israeli strain of L. major died in medium containing 50% human blood. Also, addition of 20% human blood to growth media of parasites from Israel, Kenya, or Turkemenistan caused mortality of 70 to 80% of the initial inoculum in 24 hr. At that time there was a fivefold increase in the number of Israeli parasites cultured with sand rat blood. These results imply that the vector potential and the chances of transmission are drastically decreased when man is the source of L. major parasites. (C) 1996 Academic Press, Inc.