We have previously demonstrated that lysozyme induced fusion of negatively charged phospholipid vesicles and have stressed the importance of electrostatic interactions (Posse, E. et al. (1990) Biochim. Biophys. Acta 1024, 390-394). Using centrifugation and fluorescence polarization techniques, we show, in the present paper that lysozyme interacts with negatively charged liposomes (PC/PA, 9:1), but also with neutral liposomes (pure PC). Moreover, the ionic strength and pH of the media did not modify the protein-liposomes interactions. Such interactions induce the spontaneous release of encapsulated Tb-DPA complex in liposomes. Release and fusion of PC/PA liposomes were observed. As indicated by kinetic studies and substrate curves, fusion and release are two uncoupled processes. Taking these and previous results into account we suggest a hypothetical mechanism where a relationship between aggregation, leakage and fusion of liposomes induced by lysozyme interaction is established.