Human T-cell leukemia virus type I, type II, and bovine leukemia virus (BLV) are related retroviruses which cause lymphoid malignancies in man and cattle, respectively. The etiologic role of HTLV-1 and BLV has been well established from molecular and sero-epidemiologic studies. The role of HTLV-II in human malignancy is still unclear since very few isolates of this virus have been made and until recently only one of these isolates was associated with human malignancy. Recently we have identified a second isolate of HTLV-II associated with a malignancy similar to that found in the original patient with HTLV-II. These studies provide support but do not prove an etiologic role for HTLV-II in atypical hairy-cell leukemia. As part of the studied proposed here we will further characterize this second HTLV-II isolate and its association with the patient, particularly since the patient is still alive and still has circulating leukemic cells in his peripheral blood. The virus will be molecularly clones both from the fresh leukemic cells of the patient and from cell lines we have established from this patient. Such studies are critical for understanding the role of HTLV-II in hairy-cell leukemia and will provide a conceptual and technical framework for the subsequent studies proposed in this application. These studies involve the generation of specific DNA hybridization and immunologic probes for the identification of further HTLV-II or HTLV-II-related viruses in hairy-cell leukemia and related lymphoproliferative disorders in man. It is expected that the studies proposed here will lead to the identification of novel viruses which are related to HTLV-II, much as studies of HTLV-I have led to the identification of viruses associated with acquired immunodeficiency syndrome and apparently related viruses in multiple sclerosis.