Due to the abundance of muscle, intravascular administration seems required for efficient gene or cell therapy of muscular dystrophy. Here, we examined the skeletal muscle microvasculature to assess if it is altered with dystrophin deficiency. Image analysis of capillaries was performed in three muscles of one- to ten-month-old golden retriever muscular dystrophy (GRMD) dogs and compared with healthy controls. In the gracilis muscle (and in the biceps brachii muscle) of 4- to 10-month-old GRMD dogs, the microvessel density (445+/-47 microvessels per mm(2)), the capillary to fiber ratio (111+/-26 capillaries per 100 myofibers), and the mean intercapillary distance (49+/-3 microm), were similar in affected and control dogs. The sartorius cranialis muscle in GRMD dogs showed microvessel depletion and increased intercapillary distance, but unaltered capillary to fiber ratio, relative to the controls. The mean diameter of microvessels and the total vascular area were higher in GRMD muscles than in control ones. In severely affected GRMD muscles at 7-10 months of age, fibrosis was associated with decreased microvessel density, increased intercapillary distance and microvessel diameter, but normal capillary to fiber ratio and total vascular area.