The authors have analyzed the configuration of immunoglobulin (Ig) and 8, y and 6 T-cell receptor (TCR) genes in DNA extracted from skin, lymph nodes, and peripheral blood mononuclear cells obtained from 41 patients with mycosis fungoides (MF), 14 patients with Sezary syndrome, and 13 patients with benign inflammatory dermatoses. No discrete rearranged bands (DRB) were detected in patients with inflammatory dermatoses. In tissue DNA from 19 patients with MF DRB were detected with B and y, but not 6 TCR probes. Only one patient with MF had a rearrangement of 7 and 6 with germ line B TCR genes. In 13 patients multiple biopsies were analyzed and DRB, when present, were identical in different lesions from individual patients. In three patients analysis of DNA from dermatopathic lymph nodes did not reveal DRB. Analysis of peripheral blood DNA from 24 patients revealed a discrete rearrangement of the y TCR gene in four patients and both 8 and 7 genes in four additional patients. In MF DRB were detected more frequently with advancing stage of disease in tissues ( P less than 0.01) but not in peripheral blood (P equals 0.36). Of 14 patients with Sezary syndrome, eight had DRB in peripheral blood DNA with both j3 and y probes and in three of these patients identical DRB were also detected in DNA from skin biopsy samples. In contrast, DRB were not detected in the peripheral blood of the other six patients. In both MF and Sezary syndrome there was no restricted usage of particular V y genes. These results indicate that in MF (1) T-cell clones can be detected in skin biopsy specimens from the majority of patients with early stage disease, (2) y6 T-cell clones are only rarely found, and (3) TCR gene analysis can detect T-cell clones in the peripheral blood with a greater degree of specificity than conventional light microscopic study. In Sezary syndrome these studies also suggest that a subset of patients have a polyclonal population of circulating atypical lymphoid cells. In addition these patients appear to have a better prognosis than those with monoclonal disease. Cancer 68:1572-1582,1991. YCOSIS FUNGOIDES (MF) and Sezary syndrome are M distinct clinicopathologic entities which form part of the spectrum of cutaneous T-cell lymphomas (CTCL). ' MF is a primary cutaneous lymphoma whereas Sezary syndrome is characterized by a pruritic infiltrated erythroderma, lymphadenopathy, and the presence of atypical mononuclear cells (Sezary cells) within peripheral Studies in the 1970s established that in Sezary syndrome matology, Hammersmith Hospital and St. Johns Dermatology Centre, the lymphoid are Of lineagea4 The St. Thomas' Hospital, London.atypical cells in M F have a similar morphology to Sezary * Recipient of a LORC Regional H. A. grant. cells with convoluted or cerebriform nuclei and a CD3,