The pathophysiologic events leading to toxic epidermal necrolysis (TEN) remain unknown. With the idea of an immunologically mediated reaction occurring in predisposed subjects we performed HLA-A, -B and -DR typing in 44 patients surviving TEN. We observed a significant increase of only HLA-B12, previously found associated with ocular complications of Stevens-Johnson syndrome. When patients were stratified according to the drugs involved as causes for their TEN, we found other HLA phenotypes associated with B12, varying with each category of drugs. Sulfonamide-related cases of TEN were linked to A29, B12, and DR7, while oxicam-related cases of TEN were linked to A2 and B12. These results suggest that a genetic background, related to the major histocompatibility complex, may contribute to severe blistering drug reactions.