A new family of retroviruses with potential as etiologic agents in the cause of human maligancies has been discovered. HTLV-I has been associated with a distinct form of T-cell leukemia/lymphoma (ATL). HTLV-III is the putative etiologic agent of the acquired immunodeficiency syndrome (AIDS) associated with Kaposi's sarcoma and certain forms of Hodgkin's and non-Hodgkin's lymphoma. A major focus of our research has been to characterize the relationship of this class of virus to human malignancy. Results of these studies document the close link between HTLV-I and ATL, its worldwide distribution, and tendency to be tightly clustered in close association with ATL. Modes of spread include sexual and household factors, transfusion, and possibly vector-borne transmission. Possible genetic susceptibility is also suggested. An indirect etiologic mechanism of carcinogenesis is also suggested for HTLV-I in B-cell chronic lymphocytic leukemia (B-CLL), and for HTLV-III in studies of Hodgkin's and non-Hodgkin's lymphoma and Kaposi's sarcoma. A major focus of THLV-III research has been on cohorts at high-risk for AIDS followed longitudinally since the very beginning of the AIDS epidemic. Results of these studies have documented major modes of transmission of HTLV-III in homosexual men (via receptive anal intercourse with multiple partners in high-risk areas), in hemophiliacs (via commercial plasma products), and in drug users (via frequenct needle injections). They have also documented the progression from seroconversion to subclinical immunodeficiency, to clinical manifestations (e.g., lymphadenopathy), to AIDS. Comparison of these cohorts has shown that full-blown AIDS develops in 5-20% of HTLV-III positive individuals over 32 months of follow-up. These results provide the foundation for undertaking in-depth analytic studies of these retrovirus exposure variables to better quantify these risks and the cofactors which determine the clinical outcome of exposure.