Monoclonal antibodies (moAbs) that recognize common or variable determinants of the gamma delta T-cell receptor (TcR) were used to assess gamma delta T-cell distribution on biopsy specimens and/or peripheral blood leukocytes (PBL) from 30 patients suffering from chronic cutaneous lupus erythematosus (CCLE). CD3+/gamma delta TcR + T cells were evaluated in 15 biopsies from patients with CCLE lesions, their numbers varying from 0.5 to 15.0% of all intralesional CD3 +T cells present. In all specimens from lesional skin gamma delta TCR+T cells were BB3 + and/or Ti gamma A +, indicating predominant use of the V gamma 2/V delta 2 phenotype. In the CCLE lesions the intraepidermal V gamma 2/V delta +T cells were observed in close vicinity to the damaged basal keratinocyte (KC) layer, and also randomly scattered among the densely packed inflammatory infiltrate in the dermis. In contrast to the immunohistologic findings, no numerical increase of gamma delta TcR+T cells could be observed among PBL from 28 of 30 CCLE patients. Only one CCLE patient being treated with hydroxychloroquine for two months had 15% CD3 +/gamma delta TcR+T cells among the PBL. Based on the immunohistologic findings one may infer that in CCLE, a skin-restricted form of LE, V gamma 2/V delta 2 +T cells expand extrathymically to an as yet unknown stimulus. One may also propose that these gamma delta T cells--based on their cytotoxic capacity--may contribute to the epidermal damage. It remains to be determined whether the extrathymic expansion of V gamma 2/V delta 2 +Tells occurs within lesional skin or in the periphery within subsequent recruitment into skin lesions. The results obtained by fluorescence-activated cell sorter analysis favor the first possibility.