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Leishmania donovani chagasi parasites, transmitted by sandflies of the Lutzomyia longipalpis species complex, normally cause visceral leishmaniasis. However, in Central America infections frequently result in cutaneous disease. We undertook experiments to investigate the possible influence of sandfly saliva on the course of infection. Erythemas caused by feeding sandflies correlated well with the levels of the erythema-inducing peptide, maxadilan, in their saliva. Saliva of Brazilian flies was the most potent, that of Colombian flies less so, and Costa Rican saliva had very little maxadilan and lacked activity. Nucleotide sequence differences in the maxadilan gene of the three species were detected by 'single strand conformational polymorphism' electrophoresis. Leishmania infections proliferated fastest when coinjected with the saliva of Costa Rican flies. Brazilian flies had less influence, and Colombian flies only a slight effect. Thus Costa Rican Lutzomyia longipalpis, vectors of non-ulcerative cutaneous disease, have very low vasodilatory activity and very little maxadilan, but their saliva strongly enhances cutaneous proliferation of Leishmania infections. Conversely, flies from Colombia and Brazil, vectors of visceral disease, have more maxadilan, but exacerbate cutaneous infections to a lesser degree. These coincidental observations suggest that species of Lutzomyia longipalpis differ in their propensity to modulate the pathology of the disease they transmit.