We have developed a micropipette aspiration assay to observe the lysis of large (20-30 mu m diameter) vesicles aspirated using micropipettes. Single membrane lysis events can be seen with the light microscope and are followed using fluorescence assays and video microscopy. In this study, we have examined the ability of two analogs of the fusion peptide from influenza virus hemagglutinin to induce the lysis of large unilamellar egg phosphatidylcholine vesicles, as a function of peptide concentration and pH. X31 is a wild-type peptide from one strain of Influenza A, and E5 is an analogue which has several residues replaced by glutamate residues. Both peptides were found to induce lysis of large vesicles in a pH-dependent manner. Both peptides exhibited maximal activity at pH 5, measured in terms of both rate and extent of lysis. E5 was active at much lower concentrations than X31. Our results with both peptides are compared to results published from other laboratories.