Prior studies reported increased serum or plasma creatine phosphokinase (CPK) activity in dystrophic mice from strains C57BL 6J and 129 B 6 F 1, but technique may have been a factor. In strain 129 REJ there are conflicting data with respect to CPK activities in the dystrophic mice and also with respect to any age effect on CPK activity. We compared serum CPK activity in all three dystrophic mouse strains and in a nondystrophic strain using a technique designed to eliminate or minimize muscle trauma. No significant difference in CPK activity with increasing age was noted in 129 B 6 F 1 dystrophic or normal mice or in mice from the nondystrophic strain. Strains C57BL 6J and 129 B 6 F 1 showed no difference in CPK activity between dystrophic and normal mice of the same strain. In strain 129 REJ, dystrophic mice had a significantly lower CPK activity than normal mice from the same strain. Significant interstrain differences in CPK activities for both normal and dystrophic mice were also observed among the three dystrophic strains as well as compared with the nondystrophic strain. Serum CPK activities are not elevated in mouse muscular dystrophy and, therefore, this disorder differs significantly from human dystrophy. Because of interstrain differences in CPK activities, studies using CPK activity as a dependent variable should use strain-specific controls.