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Abstract Background Recent studies suggest potential roles of immune response in the pathophysiology of epilepsy. Anti-seizure medications (ASMs) are known to have side effects of drug eruption caused by immune responses. A few reports in adults have demonstrated disappearance of seizures after an ASM drug eruption episode. In this paper, we described 2 cases of childhood absence epilepsy (CAE) who showed seizure disappearance after ethosuximide (ESM) drug eruption, suggesting the possibility that the epilepsy disappears due to immune responses to ASM. Case presentation Case 1 was an 8-year-old girl diagnosed with CAE. She was treated with valproate acid (VPA) initially, and then ESM was administered as an additional treatment. Her epileptic seizure disappeared 4 days after initiation of ESM. However, drug eruption appeared 1 week after the administration of ESM. Even after discontinuation of ESM administration, she maintains no seizure after the drug eruption. Case 2 was a 5-year-old boy diagnosed as CAE. He was treated with VPA initially, and ESM was administered additionally. Drug eruption appeared 1 month after the administration of ESM. Even after ESM was terminated, he maintained seizure freedom after the appearance of eruption. Conclusions Epileptic seizures may have been suppressed due to the immune responses caused by ASM eruption. Further studies are needed to elucidate the pathophysiologic effects of drug eruption on epilepsy through immune responses.