To evaluate bicelles as a model membrane system, we examined the morphological changes of bicelles induced by the membrane-lytic peptide melittin. P-31 NMR and dynamic light scattering experiments showed that melittin irreversibly disrupted the disk-shaped structure of bicelles and that the disrupted bicelles form giant spherical assemblies above the gel-to-liquid-crystalline transition temperature (T-m = 24 degreesC). The melittin-induced disruption of bicelles was suppressed by the addition of cholesterol, suggesting that cholesterol effectively improved the stability of the bicelle membranes in the same manner as in vesicles. Furthermore, the location of bicelle-bound melittin and its role in bicelle assembly are also discussed.