Several studies suggest increased mixed and left-handedness in schizophrenia. This is of interest as early cerebral injury can result in increased left-handedness and some investigations have suggested a role for early developmental insult (e.g., birth complications) in schizophrenia. We administered the Luria-Nebraska Neuropsychological Battery (LNNB) to 24 left-handed male schizophrenic patients and a separate group of 24 right-handed schizophrenic patients who were age and education matched to the left-handed patients. The test protocol also was administered to 15 left-handed non-psychiatric control subjects and 15 right-handed controls. Direct comparisons (t-test) of the left- to right-handed schizophrenics revealed that the left-handed patients showed significantly greater impairment on several LNNB measures sensitive to cognitive deficits in schizophrenia. There were no differences between left- and right-handed control subjects. A further 2 X 2 ANOVA pooling all subjects noted several significant interactions between handedness and diagnostic group. The findings suggest a unique interaction between left-handedness and neuropsychological impairment in schizophrenia and could support a relationship between left-handedness, early cerebral insult, and cognitive deficits.