The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes merlin, a protein with homology to the cell membrane/F-actin linking proteins, moesin, ezrin and radixin. Unlike these closely related proteins, merlin lacks a C-terminal F-actin binding site detectable by ac-tin blot overlays, and the GFP-tagged merlin C-terminal domain co-distributes with neither stress fibers nor cortochalasin tical actin in NIH3T3 cells. Merlin also differs from the other three proteins in its inter-intramolecular doand/main interactions, as shown by in vitro binding and yeast two-hybrid assays. As is true for ezrin, moesin and radixin, the N-and C-terminal domains of merlin type 1 bind to each other. However, full-length merlin and its N-and C-terminal domains, as well as the C-terminal domain of ezrin, interact with other full-length merlin type 1 molecules, and its C-terminal domain interacts inwith itself. Merlin 1 function in cells may thus depend on intra-and intermolecular interactions and their mod-ulation, which include interactions with other members of this protein family.