Background: The aim of this study was to assess working memory (WM) in patients with major depressive disorder (MDD), using a robust parametric WM task (the n-back task). Methods: Twenty patients with MDD and twenty healthy controls completed a visual version of the paradigm, comprising four levels of task difficulty (i.e. 0-, 1-, 2-, and 3-back). Performance accuracy and reaction time (RT) were measured at each difficulty level. Results: In comparison with controls, patients with MDD exhibited slower RTs (F-(1,F-38)=25.16,p < 0.001.), and reduced accuracy (F-(1,F-38)=5.93,p < 0.001). There was no diagnosis-specific effect of task difficulty on performance accuracy. However, the faster response to memory (1-3-back) than to shadowing (0-back) tasks observed in controls was not as pronounced in patients. Conclusions: These observations support a relatively specific impairment of WM/central executive function in MDD, which may potentially mediate the diverse pattern of cognitive dysfunction noted in MDD. The parametric n-back task is applicable to subjects with MDD and yields results interpretable across the dimensions of task difficulty and performance in controls and patients. (c) 2005 Elsevier B.V. All rights reserved.