OBJECTIVE To characterize interhemispheric functional and anatomic connectivity in patients with idiopathic generalized epilepsy and generalized tonic-clonic seizures (GTCS). METHODS This retrospective study was approved by the local institutional review board and was HIPAA compliant. All participants provided written informed consent. Resting-state functional and structural magnetic resonance images were acquired in 52 patients with GTCS and 65 healthy control subjects. The functional connectivity between bilateral homotopic voxels was calculated. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for an analysis of diffusion-tensor imaging tractography. The fractional anisotropy and fiber length were compared between groups. Two-sample t test and nonparametric correlation analysis were used. RESULTS Compared with control subjects, patients showed increased interhemispheric functional connectivity between the bilateral cuneus (P = .0008, corrected) and anterior cingulate cortex (P = .0003, corrected) and decreased functional connectivity between the bilateral olfactory cortex (P = .00005, corrected), inferior frontal gyrus (P = .00005, corrected), supramarginal gyrus (P = .0002, corrected), and temporal pole (P = .0003, corrected). Furthermore, the fiber length of the commissural fiber bundles connecting the bilateral anterior cingulate cortex (t = -2.30; P = .03, uncorrected) and the bilateral cuneus was shorter in patients than in control subjects (t = -3.19; P = .002, uncorrected). CONCLUSIONS Our findings show that the bilateral anterior cingulate cortex may be critical to the pathophysiology of patients with GTCS and suggest that the corresponding commissural fiber bundle in the genu of the corpus callosum is a potential target for future surgical treatment in patients with intractable GTCS.