Reductions in the size of the corpus callosum (CC) have been described in patients with bipolar disorder (BD), although the contribution of genetic factors to these changes is unclear. We previously showed a global thinning of the CC in BD patients, and found those with a family history of affective disorders had a larger CC than those without. In this study, we compared callosal size and shape in 180 individuals: 70 with BD, 45 of their first-degree relatives, and 75 healthy controls. The callosum was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images, and its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points. Validating our previous findings, a significant global reduction in callosal thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in callosal size or shape from controls. In BD patients, duration of illness and age were associated with thinning in the anterior body; BD patients on lithium treatment showed a thicker anterior mid-body than those on other psychotropics. Global and regional thinning of the callosum is seen in BD but not in their first-degree relatives. This suggests that CC abnormalities are linked to disease expression in BD and may not represent a marker of familial predisposition.