Our aim was to determine whether recombinant human growth hormone (rhGH) administration might modulate the enzyme degradative capacity of the muscle lysosomal system and influence muscle growth. Muscle cathepsin D, acid RNase and DNase II activities were determined in the gastrocnemius muscle of rhGH-treated post-weaning female BALB/c mice. Linear regressions were used to analyze the relationships of each enzyme with their respective substrate. Exogenous GH provoked a depletion-recovery response of muscle growth with a catch-up growth like mechanism. Cathepsin D activity decreased with age in all animals (GH: 40%; saline: 79%), showing a substantial developmental decline that could reflect changes in the rate of protein breakdown. However, the degradative capacity of cathepsin D was unmodified in rhGH-mice compared with saline mice (according to the enzyme vs substrate linear regression slope). In contrast, acid RNase and DNase II activities directly participated in muscle RNA and DNA degradation. Both nucleases were inhibited by GH treatment (48% and 63% decreases, respectively, vs. saline at 50d). The decrease in RNase activity suggests an inverse relation between the rate of protein synthesis (high) and acid RNase activity (low), leading to spare muscle RNA for synthesizing protein during catch-up growth. Also, the low DNase II activity could contribute to inhibiting of muscle DNA degradation, facilitating muscle growth. GH seems to act as a direct modulator of the degradative capacity of skeletal muscle nucleases, influencing DNA and RNA degradation during the depletion-recovery response to GH of gastrocnemius muscle in post-weaning mice.