This study investigated the associations between (1) handedness (demonstrated preference of one hand for the performance of most unimanual tasks) and neuroanatomical asymmetry (measurable differences in width between the cerebral hemispheres) and (2) familial history of handedness (the presence of a left-handed sibling or parent of a right-handed subject) as an intervening factor in the relation between handedness and neuroanatomical asymmetry. Width measurements of the brain were derived from computerized tomographic ( CT) films and grouped in to categories by hand preference (measured by the Edinburgh Handedness Inventory) and family history. The measurements of right (n=68), right with left-· handed relatives (n=24), and left-handed (n=16) groups were then compared by width and other transformations of the brain measurements. Subjects were adults of both sexes who had been referred for neurologic examination and were diagnosed as free of major distorting brain pathology. Hemispheric widths were compared by group, as ratios (left÷right) and as differences (left-right). Analysis of variance revealed significant differences between right-hemisphere widths at three percentages of brain length in the posterior occipital and temporal-parietal portion of the right hemisphere. The two right-handed groups had significantly smaller right-hemisphere measurements than the left group at 80% (p=.03), 75% (p= .012), and 60% (p= .029) of brain length. There were no significant left-hemisphere differences between the groups. In terms of ratios of sides and differences between sides in the same brain region, the left - handed group was different from the right-handed group at the p Handedness appears to be moderately associated with neuroanatomical asymmetry. The differences in sizes of brain structures and their relation to functionally lateralized abilities may shed light on the processes by which each hemisphere becomes specialized to perform specific tasks and other aspects of individual differences.