The ability of three populations of Phlebotomus papatasi collected from different areas of Egypt (Sinai, Aswan and Delta regions) to acquire successfully and transmit Leishmania major (Sinai sandfly isolate IPAP/EG/89/SI-177) was evaluated in the laboratory. Flies from each population were fed artificially on infected blood suspensions, using a chick-skin-membrane feeding apparatus, and naturally on infected mice. Samples of fed flies were dissected and examined microscopically to determine the infection rate and intensity of parasite infection. The Aswan population had a significantly lower feeding rate (16.2%) than the Sinai (51.2%) and Delta (69.7%) populations (P < 0.0001). The infection rate for the Sinai population was significantly higher (65.9%) than the rate for the Delta (52.3%; P < 0.05) and slightly higher than that for the Aswan (62.5%). No differences were observed in the intensity of L. major infection in the midguts of the sandflies examined from any of the three populations. When flies from each population were fed naturally on BALB/c mice infected with L. major, the feeding rates of the three populations showed a similar pattern to that seen in the membrane feeds, with the Aswan population having the lowest rate. In each of two separate trials for each population, a group of artificially infected flies was refed on uninfected BALB/c mice. Thirty-six days following exposure to the infected sandflies in the Sinai population, a leishmanial lesion was observed on the corner of one animal's mouth. These observations provide the final piece of evidence that P. papatasi is a vector of L. major in Egypt.