Several decades of research have led to different hypotheses about cognitive functioning in depression; one of the hypotheses states that there is altered functioning of the hemispheres during a depressive episode. Lateralization studies have found diminished neuropsychological functioning in depressive patients; especially right-hemisphere functions seem impaired. In our study we used conventional neuropsychological tests to study shifts in hemispheric functioning. Neuropsychological testing before and after therapy in 52 (for the most part therapy-resistant) depressives showed no substantial effects in lateralized functioning. None of the measures enabled prediction of response to treatment; however 17 different interaction variables were identified, five of which make an unique contribution.