Muscular dysgenesis (mdg) in the mouse is an autosomal recessive lethal disorder that is manifested by a gross failure of skeletal muscle development. In vitro mdg/mdg myoblasts proliferate normally and fuse successfully into myotubes, but these myotubes fail to contract either spontaneously or in response to physiological stimuli despite the presence of effective contractile elements and an ability to propagate action potentials normally. We have determined that mdg/mdg and +/+ myoblasts are capable of fusing in vitro to form "mosaic" myotubes which typically express an apparently normal contractile phenotype. Electrophoretic analysis of the relative activities of myotube glucosephosphate isomerase (GPI-1) isozymes provided a means of estimating the proportions of myonuclei of each genotype within individual myotubes. Only a very small proportion of genotypically normal myonuclei were required for expression of an apparently normal contractile phenotype.