Expression of -catenin is known to be important for developmental processes such as embryonic pattern formation and determination of cell fate. Inappropriate expression, however, has been linked to pathological states such as cancer. Here, we report that expression of -catenin is necessary for physiological growth of skeletal muscle in response to mechanical overload. Conditional inactivation of -catenin was induced in control and overloaded muscle through intramuscular injection of adenovirus expressing cre recombinase in the -catenin floxed mice. Individual muscle fiber analysis was performed to identify positively transfected/inactivated cells and determine fiber cross-sectional area. The results demonstrate that fiber growth is completely inhibited when the -catenin expression is lost. This effect was cell autonomous as fibers that did not exhibit recombination in the floxed mice grew to the same magnitude as infected/non-infected fibers from wildtype mice. These findings suggest that -catenin may be a primary molecular site through which multiple signaling pathways converge in regulating physiological growth.