The possible involvement of the human T lymphotropic viruseswith T-PLL is also complicated by the inconsistent classi- LGL leukemia is also rare and, unlike T-PLL or ATLL, the involvement is a frequent feature of T prolymphocytic leukemia (T-PLL) and antibodies against HTLV-I and -II have been malignant cell usually has a CD4 − CD8 + or, rarely, a natural and -II in T-PLL and LGL leukemia, we investigated 64 such reverse transcriptase assay patients for the presence of HTLV-I/II by serology and molecular techniques using PCR primers against HTLV-II and all parts of the HTLV-I genome. The sensitivity of the technique was Introduction increased by using nested PCR. Reverse transcriptase (RT) activity was also measured in supernatants from peripheral The human T cell lymphotropic virus type I (HTLV-I) was first blood mononuclear cells (PBMCs) in short-term culture (STC). isolated from a patient with a mature CD4 + T cell lymphoproliferative disorder subsequently diagnosed as adult T cell leukemia/lymphoma (ATLL). 1 A related retrovirus, HTLV-II, Patients and methods was later isolated from cell lines from two patients thought to have a T cell variant of hairy cell leukemia. 2,3 This led to a hunt for the retrovirus in other mature T cell lymphoproliferPatients ative disorders. A few groups have reported the presence of HTLV-I sequences in seronegative cases of cutaneous T cell T-PLL is a lymphoproliferative disorder of mature (TdT+) T lymphoma (CTCL), although the proportion of positive cases cells characterized by splenomegaly, lymphadenopathy, fredocumented varies widely and findings remain controquent skin involvement and circulating abnormal prolymphoversial. 4,5 T prolymphocytic leukemia (T-PLL) shares some cytes (often greater than 200 × 10 9 /l) whose phenotype is usuclinical and histopathological features with ATLL, namely skin ally CD4 + CD8 − . The diagnostic features of LGL leukemia are infiltration, aggressive course and a CD4 + phenotype of maliga sustained lymphocytosis Ͼ4 × 10 9 /l with Ͼ80% of lymphonant lymphocytes in two-thirds of cases. 6 However, T-PLL is cytes showing prominent azurophilic granules, neutropenia or a rare disorder representing only around 3% of mature B and other cytopenia not related to heavy bone marrow infiltration, T cell leukemias 7 and few cases have been studied for eviand predominance of a discrete T cell or natural killer subset dence of HTLV-I or -II infection using a range of sensitive techby membrane marker analysis, commonly CD3 + CD4 − CD8 + niques. The question of whether HTLV-I or -II is associated or CD3 − CD4 − CD8 − CD16 + CD56 + , respectively. Sixty-four patients were studied, 36 with T-PLL and 28 with LGL leukemia, three of the latter having NK phenotype. Serology for HTLV-I/II by ELISA and particle agglutination, performed at the PHLS Reference Laboratory, Colindale, London,