Glucocorticoid use may provide short-term functional improvement in boys with Duchenne muscular dystrophy (DMD). We report functional and histopathologic changes following a 4-month course of daily oral prednisone in a canine model of DMD, termed golden retriever muscular dystrophy (GRMD). Muscle extension forces in GRMD dogs treated daily with 1 and 2 mg/kg prednisone measured 2.349 +/- 0.92 and 3.486 +/- 0.67 N/kg, respectively, compared to 1.927 +/- 0.63 N/kg in untreated GRMD controls (p < 0.05 for 2 mg/kg group); GRMD muscle flexion forces measured 0.435 +/- 0.13 and 0.303 +/- 0.08 N/kg, respectively, compared to 0.527 +/- 0.01 N/kg in untreated GRMD controls (p < 0.05 for both groups). Although cranial sartorius hypertrophy and tibiotarsal joint angles also tended to improve, myofiber calcification increased and fetal myosin expression decreased following prednisone. Thus, functional data indicate benefit but histopathologic changes following prednisone treatment in GRMD suggest possible deleterious consequences.