Introduction: In this study we sought to: (1) determine the distribution of GABA(A) receptors (GABA(A)-Rs) in the brain of Duchenne muscular dystrophy (DMD) patients; and (2) ascertain if the distribution pattern correlates with cognitive dysfunction. Methods: Fourteen DMD patients [young adult (n = 7, 18-25 years old) and older adult (n = 7, 30-37 years old) groups] and 16 age-matched normal volunteers participated. GABA(A)-R distribution was assessed using I-123-IMZ-SPECT. Neuropsychological assessments were performed using 3 different test batteries, the WAIS-III, WMS-R, and Wisconsin Card Sorting Test (WCST). Results: All DMD patients showed significant decline in I-123-IMZ uptake in the prefrontal cortex (P < 0.05). Although no differences were detected in the WAIS-III and WMS-R, the WCST scores of DMD patients (2.8 +/- 1.9) were significantly lower (P < 0.01) than those of normal volunteers (5.4 +/- 0.7). Both abnormalities were more pronounced in older adult patients. Conclusion: The findings demonstrate that DMD is accompanied by a reduction in the prefrontal cortex distribution of GABA(A)-Rs.