Salivary gland homogenates (SGH) of female Lutzomyia longipalpis, in concentrations as small as 0.05 pairs of glands/ml, inhibit the in vitro multiplication of promastigotes of Leishmania mexicana amazonensis. The effect seems to be cytostatic since promastigote viability 24 hr after exposure ranged from 55% to 100% in different experiments. The cells cultivated in the presence of SGH were characterized by a very slender shape, with cell bodies that were almost two times as long as controls. The promastigote growth inhibitory activity was not present in Anopheles albimanus SGH or in the gut extracts of Lu. longipalpis sand flies. Additionally, the salivary gland homogenates of Lu. longipalpis did not inhibit the growth of other cell types such as Escherichia coli or a monkey kidney cell line (LLCMK2), suggesting that the activity had a specific range of action. The SGH activity was sensitive to both trypsinization and boiling, partially resistant to heating at 56°C for 30 min, and had a molecular weight of approximately 20 kD as determined by size exclusion high-performance liquid chromatography. The results suggest that vector saliva could influence the development of Leishmania parasites within the vector by inhibiting their growth and triggering them to a differentiation pathway.