Neuropsychological deficits have been associated with major depression (MD) and persist in some individuals even after symptom remission. However, it is unclear if the deficits are a consequence of MD or are pre-existing and reflect MD vulnerability. We addressed this issue by studying 117 twins from monozygotic (MZ) pairs discordant for lifetime history of DSM-III-R defined MD and 41 twins from MZ pairs in which neither twin had experienced MD. Our assessment included a structured clinical interview and measures from the WMS-III and WAIS-III. The "unaffected" twins from discordant pairs showed the same pattern of performance as their affected cotwins on measures of attention, working memory, verbal memory, and visuo-spatial processing. Compared to twins from pairs with no MD history, twins in discordant pairs had lower performance in the domains of attention, memory, visuo-spatial processing, and general knowledge. However, after adjusting for sex and age, the groups differed only on attention and general knowledge. The similar performance of twins in pairs discordant for MD suggests that familial risk for MD has a greater influence on neuropsychological functioning than individual MD history. Findings of impairment in individuals euthymic for MD are more consistent with pre-existing deficits than scarring effects of MD.