Agrin is believed to be a factor used by motoneurons to direct acetylcholine receptor (AChR) clustering at the neuromuscular junction. However, exactly how agrin mediates this effect remains unclear. Here we demonstrate that the beta-catenin interacts with rapsyn, a molecule key for AChR clustering. Agrin stimulation increases the association of beta-catenin with surface AChRs. Suppression of beta-catenin expression inhibited agrin-induced AChR clustering, suggesting a necessary role of beta-catenin in this event. The beta-catenin action did not appear to require the function of T-cell factors (TCFs), suggesting a mechanism independent of TCF-mediated transcription. In contrast, prevention of beta-catenin from interacting with alpha-catenin attenuated agrin-induced AChR clustering. These results suggest that beta-catenin may serve as a link between AChRs and alpha-catenin-associated cytoskeleton, revealing a novel function of beta-catenin in synaptogenesis.