Megalin is multiligand receptor heavily involved in protein endocytosis. We recently demonstrated that megalin binds and mediates internalization of Ang II. Although there is strong structural resemblance between Angiotensin (Ang) II and Ang-(1-7), their physiological actions and their affinity for the AT₁R are dissimilar. Therefore, the hypothesis of the present work was to test if megalin binds and internalizes Ang-(1-7). The uptake of Ang-(1-7) was determined by exposure of confluent monolayers of BN/MSV cells (a model representative of the yolk sac epithelium) to fluorescently-labeled Ang-(1-7) (100 nM) and measurement of the amount of cell-associated fluorescence after 4 hours by flow cytometry. Anti-megalin antisera and an AT₁R blocker (olmesartan) were used to interfere with uptake via megalin and the AT₁R respectively. Ang-(1-7) uptake was prevented by anti-megalin antisera (63%) to a higher degree than olmesartan (13%) (p < 0.001). In analysis by flow cytometry of binding experiments performed in brush border membrane vesicles isolated from kidneys of CD-1 mice, anti-megalin antisera interfered with Ang-(1-7) binding more strongly than olmesartan (p < 0.05 against positive control). Interactions of megalin with Ang-(1-7) at a molecular level were studied by surface plasmon resonance, demonstrating that Ang-(1-7) binds megalin dose and time-dependently and with an affinity similar to Ang II. These results show that the scavenger receptor megalin binds and internalizes Ang-(1-7).