The anticonvulsant drug hypersensitivity syndrome (AHS) is a potentially fatal drug reaction associated with aromatic antiepileptic drugs, the pathogenic mechanisms of which are still unclear. We studied a 2-year-old female affected with AHS after phenobarbital treatment. In vitro experiments showed a T-lymphocyte response to the drug and an increased, dose-related, IL-6 production after drug incubation. These findings suggest that AHS may be caused by a T-lymphocyte dependent mechanism, involving pro-inflammatory cytokines.