A 54-year-old white man with chronic renal failure developed toxic epidermal necrolysis (TEN) due to an infection by Staphylococcus aureus of phage type 2. Analysis of host defenses in this patient revealed normal humoral immunity and neutrophil functions, but a deficiency in cell-mediated immunity. This deficit was characterized by negative delayed skin tests, no sensitization to 2,4-dinitrochlorobenzene, no phytohemagglutinin stimulation of peripheral lymphocytes, and inability of the patient's lymphocytes to release macrophage aggregation factor. This deficiency may have contributed to the development of the syndrome. It should be recognized that TEN may occur in an adult secondary to staphylococcal infections and that therapy with a penicillinase-resistant penicillin is needed.