Erythema multiforme (EM) is an immune-mediated disease categorized into EM minor and EM major, also called Stevens-Johnson syndrome. The presence of mucosal involvement differentiates erythema multiforme major from erythema multiforme minor. Many drugs and agents can induce Stevens-Johnson syndrome. We report a case of Stevens-Johnson syndrome associated with Mycoplasma pneumoniae infection. Lymphopenia with a significant decrease of CD4+ T cells in the blood and predominant CD4+ T cells in the skin vesicular fluid was found. The improvement of lymphopenia was associated with disease recovery. In a retrospective chart review of patients treated in our hospital over the past 3 years, we found that 5 patients with Stevens-Johnson syndrome all had lymphopenia (< 1.50 x 10(9)/L; average 0.99 x 10(9)/L), whereas 13 other patients with erythema multiforme minor demonstrated normal lymphocyte counts (average 3.13 x 10(9)/L), with the exception of one patient with herpes infection showing lymphopenia. These results suggested that an immunopathogenesis involving redistribution of CD4+ T cells might contribute to the development of Stevens-Johnson syndrome. Further studies to investigate the involvement of CD4+ T cells in Stevens-Johnson syndrome may implicate a specific strategy to prevent fatal Stevens-Johnson syndrome.