Transient neuroimaging abnormalities associated with seizure activity have received little attention in the literature. The authors report a focal magnetic resonance (MR) imaging abnormality of the corpus callosum in a patient following a secondary generalized seizure. A 27-year-old right-handed man presented with a history of medically refractory partial seizures since the age of 1 year. The results of an MR imaging study obtained 4 months prior to the patient undergoing video-electroencephalography monitoring were unremarkable. After the patient discontinued all antiepileptic medications, a secondary generalized seizure of right temporal origin was recorded. Five days later, repeated MR imaging revealed a nonenhancing 14 x 11-mm ovoid hyperintense lesion in the splenium of corpus callosum. The patient was asymptomatic, and his neurological and neurocognitive examinations remained unremarkable. Follow-up MR imaging 5 weeks and 1 year later demonstrated near-complete resolution of the lesion. Benign and transient abnormalities in the splenium can occur as a periictal phenomenon. A high index of suspicion and follow-up imaging may prevent further unwarranted intervention.