Purpose: Pharmacological evidence suggests abnormalities in the brain serotonin (5-HT) system in obsessive–compulsive disorder (OCD) involving cortical 5-HT2A receptors. However, recent animal and human studies have also implicated the glutamate system in OCD. Animal studies found that disrupting glutamatergic signaling at cortico-striatal synapses leads to OCD-like behaviors, human genetic studies demonstrated associations between the glutamate transporter SLC1A1 and OCD, and case studies and open label trials demonstrated efficacy of glutamatergic agents in reducing OCD symptoms. This has led to the hypothesis that OCD symptoms result either directly or indirectly from increased glutamatergic signaling in cortico-striatal pathways. As 5-HT2A receptors are located on both pyramidal cells and interneurons and may modulate glutamate and GABA transmission, we measured 5-HT2A receptor availability with PET, and Glx (glutamate plus glutamine) and GABA levels with MRS in OCD patients and matched controls.