Extracts of salivary glands of the yellow fever mosquito Aedes aegypti inhibit tumour cell-stimulated release of tumour necrosis factor alpha (TNF alpha) from rat mast cells, but do not inhibit antigen-induced histamine secretion. This inhibitory activity for TNF alpha is found in salivary glands of female but not in male mosquitoes. This inhibition is not mediated by bacterial contamination (LPS), by calcitonin gene related peptide (CGRP), nerve growth factor (NGF), epidermal growth factor (EGF) or transforming growth factor beta (TGF beta). The factor(s) has a molecular weight > 10 kDa and is neutralized by boiling for 10 min or heating at 56 degrees C for 30 min. The modulation of this proinflammatory mediator, TNF alpha, produced by mast cells in sites of blood feeding may facilitate completion of the blood meal, and as reported for certain vector-transmitted parasites, may enhance infectivity.