This study was designed to identify the types of neuropsychological deficits that are unique to familial and nonfamilial forms of schizophrenia. Seventy-two patients who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder, mainly schizophrenic, were divided into two groups on the basis of the presence or absence of a family history of psychosis. The two groups were then compared for differences on six neuropsychological parameters as well as for differences in psychotic symptoms. Multivariate analyses indicated that schizophrenic patients with a family history of psychosis showed significantly higher levels of overall neuropsychological deficit and significantly greater deficits on tests of motor-control and abstraction and problem-solving. Factor analyses indicate that schizophrenic patients with a family history of psychosis show a pattern of specific neuropsychological deficits, while schizophrenic patients without a family history show a pattern of more consistent cognitive deficits. The results of this study indicate that recent-onset schizophrenic patients with and without a family history of psychosis show distinctly different patterns of neuropsychological dysfunction. These data suggest that abnormalities in the dorsolateral prefrontal cortex and nonprimary motor areas may be associated with an increased familial risk for psychotic disorder.