Muscle progenitors in Xenopus interact in a community of 100 or more cells to activate their myogenic genes and the muscle differentiation pathway. We examine whether the cell adhesion molecule cadherin is involved in this process. Injections of dominant negative N-cadherin RNA into the region of 2- to 4-cell embryos that will give rise to muscle suppress MyoD expression in muscle progenitor cells. By contrast, Xbra expression is unaffected and levels of Xwnt-8 message rise with increasing doses of dominant negative cadherin RNA. MyoD inhibition in embryos injected with the dominant negative cadherin mRNA is rescued by coinjection of full-length cadherin RNA, showing that the inhibition of MyoD occurs through the cadherin pathway. These results show that cadherin-mediated cell interactions play a critical role in the signaling events required for muscle progenitor cells to differentiate, as judged by their stable activation of MyoD.