Serum creatine-kinase (CK) activities were determined in 536 patients affected with X-linked muscular dystrophy (456 with Duchenne or DMD and 80 with Becker or BMD) and serum pyruvate-kinase (PK) in 360 among them (309 DMD and 51 BMD). The aim of this investigation was to assess the variability and rate of decrease in serum activity in DMD as compared with BMD as a function of age and in DMD as a function of Vignos scale as well. In DMD, maximum CK and PK activities were found around 1-6 years old and the average rate of decline according to age was estimated as 0.18 per year and 0.27-0.29 for both enzymes as a function of Vignos scale (assessed in 291 cases). For BMD, maximum serum enzyme levels were found around 10-15 years old and the rate of decline of serum activity per year was 0.06 for CK and 0.07 for PK. If maximum levels of serum enzyme reflect active muscle degeneration and the rate of decline per year to progressive loss of muscle mass (responsible for the release of muscle enzymes to the blood stream) our observations suggest: (a) active muscle degeneration occurs, on average, 5 years later in the group of outliers and 10 years later in BMD as compared with severe DMD; (b) the rate in which muscle mass is lost is significantly greater in DMD than in BMD and therefore serum enzyme determinations may represent an important test for evaluation of therapeutic trials; (c) serum enzymes determination may represent an important preliminary test to discriminate in a proportion of young patients if they will develop a severe or milder phenotype.