The neurofibromatosis type II (NF2) tumor suppressor gene is inactivated in the development of familial and sporadic schwannomas and meningiomas. The encoded protein, merlin, is closely related to ezrin, radixin, and moesin, which are members of the band 4.1 family of membrane/cytoskeletal linker proteins. We have examined the localization and effects of overexpressing epitope-tagged full-length isoforms of merlin as well as amino- and carboxyl-terminal truncations. The full-length and the amino-terminal domain of merlin localize to cortical actin, particularly areas of dynamic actin rearrangements such as membrane ruffles. Furthermore, overexpression of the carboxyl half of merlin induces cell death in NIH3T3 cells. The effect is splice-form specific and is not observed in the context of the full-length molecule. Thus, as has been described for the erzin, radixin, and moesin proteins, the activities of the carboxyl-terminal domain of merlin may be suppressed by the amino-terminal domain.