Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls. Method: Single-voxel proton magnetic resonance spectroscopic examinations of the anterior cingulate cortex were conducted in 14 psychotropic-naive children and adolescents with MDD without OCD, 10 to 19 years of age, 14 case-matched healthy controls, and 20 nondepressed, psychotropic-naive pediatric patients with OCD 7 to 19 years of age. Results: Anterior cingulate glutamatergic concentrations were significantly reduced in both patients with OCD (15.1% decrease) and patients with MDD (18.7% decrease) compared with controls. Anterior cingulate glutamatergic concentrations did not differ significantly between patients with OCD and those with MDD. Conclusions: Altered anterior cingulate glutamatergic neurotransmission may be involved in the pathogenesis of OCD and MDD. These preliminary findings further suggest that reduced anterior cingulate glutamate does not differentiate pediatric patients with OCD from pediatric patients with MDD. J. Am. Acad. Child Adolesc. Psychiatry, 2004;43(9):1146-1153. Key Words: obsessive-compulsive disorder, depression, proton magnetic resonance spectroscopy, anterior cingulate, glutamate.