2F5, a monoclonal antibody that neutralizes HIV-1 primary isolates, recognizes an epitope in the membrane proximal region of the glycoprotein gp41 ectodomain. It is believed that binding to the viral membrane is a step in the antibody mode of action, as usual in ligand membrane receptor interactions. We investigated the interaction of 2F5 with membrane model systems, namely large unilamellar vesicles, by means of fluorescence techniques. There were no significant interactions of 2F5 with model viral membranes or with model target cell membranes. Thus, the usual three-step 'membrane catalysis' method is not followed by 2F5 in its mode of action.