Ca2+ has a central role in various cellular phenomena involving membrane fusion. However, little is known about the mechanisms involved. Model membrane systems such as phospholipid vesicles have been used extensively to study the mechanism of membrane fusion at the molecular level. For example, phosphatidylserine (PS) vesicles have been shown to undergo massive aggregation and structural rearrangements on additon of Ca2+, with eventual formation of large cochleate structures. Although these structures do not retain appreciable internal volume, their formation has been proposed to result from fusion of the initial vesicles. The significance of the PS--Ca2+ system as a model for biological membrane fusion has been questioned recently by Ginsberg. Based on the observation that divalent cations induce the release of contents from PS vesicles but fail to bring about the uptake of a marker from the medium, he proposes that the vesicles are ruptured completely during interaction with divalent cations and reassemble subsequently to form large non-vesicular structures. The present study demonstrates that the question raised by Ginsberg is not particularly relevant to the phenomenon concerned, and that his experimental observations do not allow the exclusive conclusion that Ca2+ induces lysis of PS vesicles rather than fusion.