The CANTAB battery of neuropsychological tests was used to compare the performance of 28 patients with unipolar depression with that of 22 age and IQ matched controls. The patients were impaired on almost all tests studied with deficits in pattern and spatial recognition memory, matching to sample, spatial span, spatial working memory and planning. Most of the patients showed at least some impairment and deficits were seen across cognitive domains. An important finding was the detrimental effect of failure on subsequent performance; having solved one problem incorrectly, patients were far more likely than controls to fail the subsequent problem. Superimposed on the general deficits, there were also specific deficits in executive tasks characteristic of frontostriatal dysfunction and deficits in mnemonic tasks characteristic of temporal lobe dysfunction. This combination of a specific form of motivational deficit, resulting in oversensitivity to negative feedback, and superimposed specific neuropsychological deficits were correlated with severity of depression. The most significant correlations were seen between mnemonic deficits and clinical rating scores. Comparisons of the deficits seen in the depressed patients in this study with other patient groups assessed with the CANTAB neuropsychological battery, showed that one of the hypotheses of the neuropsychological deficits in depression, that of ‘frontosubcortical’ or ‘frontostriatal’ dysfunction, was not supported. These findings are discussed in relation to the likely neural substrates of depression.