The development of lesions in dogs with canine X-linked muscular dystrophy (CXMD) was studied in dogs from birth to 8 weeks of age. Selective involvement of muscles was noted in dogs up to 4 weeks of age, after which lesions were noted in all muscles examined. Marked fiber hypertrophy was a consequence of the dystrophic process. Severe degenerative lesions were first detected in the tongue, diaphragm, trapezius, deltoideus, extensor carpi radialis, sartorius, and cranial tibial muscles, with relative sparing of the triceps, biceps femoris, and quadriceps muscles. Fiber necrosis and regeneration were present in the tongue muscle at birth, indicating onset of degeneration in utero. The propensity for early development of lesions in certain muscles could not be attributed to larger fiber diameter or to fiber maturity. It is suggested that early development of lesions in these muscles may be related to the activity of these muscles in neonatal dogs.