A 4-year-old Japanese boy with Rothmund-Thomson syndrome suffered from severe herpes encephalitis at 5 months of age. The serum level of immunoglobulin G was low and the responsiveness of peripheral blood mononuclear cells to bacterial superantigens was poor. It was suggested that these immunological abnormalities, possibly associated with Rothmund-Thomson syndrome, led to severe infection with herpes simplex virus in our patient.