Aim of the study was to identify neuropsychological predictors of the clinical response to cognitive behavioral therapy (CBT) in patients with major depression. 19 unmedicated patients underwent neuropsychological testing at baseline and subsequently were assigned randomly to CBT over 3 weeks either as monotherapy or combined with sleep deprivation (SD) therapy (two nights of total SD / week). Hierarchical regression analysis revealed that parameters of declarative verbal memory and a word fluency task predicted the clinical response (percentage improvement of Hamilton depression scores) to CBT monotherapy, whereas no such prediction was obtained in the combination group. The results suggest that certain cognitive performances have a unique predictive value for the response to CBT, which appears to be abolished by additive treatments with cognitive side effects (e. g. SD).