This study examined the neuropsychological and personality functioning of four groups of “normal” subjects: (1) “clean”; (2) positive drug screen; (3) prior psychiatric diagnosis; and (4) first-degree relative with a psychiatric history. Researchers usually exclude these latter three groups based on the assumption that their neuropsychological functioning will be worse than “clean” normal subjects. Of the four groups, there was a trend for the drug group to perform worse on neuropsychological tasks and for subjects with a personal or family history of psychiatric disorder to perform better. Within the drug group, the five subjects who tested positive for cocaine or barbiturates showed worse performance than the marijuana group. Thus, it appears that it is important to screen normals for drugs, especially for cocaine and barbiturates, because of adverse neuropsychological performance.