Female Aedes aegypti that were given a blood meal by enema deposited yolk in their oocytes and synthesized trypsinlike enzymes in their midgut. When females were given an enema of Aea-TMOF (Trypsin Modulating Oostatic Factor) (NH2-YDPAPPPPPP-COOH) and blood both egg development and trypsin biosynthesis were inhibited. Similar results were observed if TMOF was mixed with the blood meal and fed to female mosquitoes through a membrane. Renin inhibitor (NH2-PHPFHFFVYK-COOH) or poly proline given by enema with the blood meal did not affect egg development or trypsin biosynthesis. Feeding of TMOF analogs P1 (NH2-YDPAP-COOH) or P4 (NH2-YDPAPPPP-COOH) inhibited trypsin biosynthesis in the midgut. Injecting or giving an enema of an amidated peptide (NH2-WRPGPPPPPP-CONH2) of HIV-2 X-ORF protein also inhibited egg development and trypsin biosynthesis in the mosquito gut. When [3H]TMOF was purified by high performance liquid chromatography (HPLC) and fed with the blood meal through a membrane to female mosquitoes, [3H]TMOF outside the gut increased linearly for the first 24 h and 28% of the hormone was found outside the gut at 72 h. These results suggest that TMOF and its active analogs traverse the gut epithelial cells into the hemolymph, bind TMOF gut receptor(s) and modulate trypsin biosynthesis.