Despite being the most effective treatment available, as many as one third of patients who receive exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) do not initially respond to treatment. Recent research suggests that the n-methyl d-aspartate (NMDA) receptor partial agonist D-Cycloserine (DCS) may speed up the course of ERP for OCD rather than enhance it. Thus, it is unclear whether DCS would benefit patients who have proven nonresponsive to ERP and serotonin reuptake inhibitors. The present study evaluated the ability of DCS to enhance ERP for 2 patients with OCD who previously had failed to show adequate response to treatment using time-series analysis. Both patients experienced greater reductions with DCS augmented ERP than they did with prior treatment; however, 1 patient relapsed by the 1-month follow-up. DCS augmented ERP might be an effective method for boosting outcomes in individuals who do not readily respond to ERP. (Contains 2 figures.)