Previous studies on alpha-lactalbumin induced fusion of phosphatidylserine/phosphatidylethanolamine vesicles are extended to vesicles composed of various combinations of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine and cardiolipin. It was found that inclusion of phosphatidylcholine in the vesicles results in a depression of fusion. This depression of fusion appears to be caused by a reduction in the amount of irreversibly bound alpha-lactalbumin to vesicles containing phosphatidylcholine. It is suggested that in this system fusion is dependent upon the extent by which a particular protein segment penetrates the bilayer.