We have investigated the protein turnover modulations involved in the hypertrophic muscle phenotype of c-ski overexpressing transgenic mice. In these animals, the body weight is increased and all the muscles examined show a definite hypertrophy. The protein degradation rate is significantly reduced in the fast twitch muscles of c-ski transgenic animals with respect to controls; in contrast, there are no detectable differences in the synthesis rates. The down-regulation of protein breakdown is paralleled by decreased expression of genes belonging to the lysosomal as well as to the ATP-ubiquitin-dependent proteolytic pathways.