The retroviruses known as Human T-Lymphotropic Virus Types I and II (HTLV-I and -II) were recognized before the human immunodeficiency virus (HIV-1). Associated diseases of HTLV-I infection, including a particular kind of leukemia or the development of a specific demyelinating disease, have also been observed. Screening of blood donors for antibodies to HTLV was mandated in November of 1988. This paper examines the biology of HTLV-I and HTLV-II and reviews the testing methods for HTLV-I/II. Data from 39,908 blood donations of volunteer donors at The University of Texas M. D. Anderson Cancer Center (UTMDACC), Division of Laboratory Medicine, Section of Transfusion Medicine are presented. Initially reactive specimens for HTLV antibodies were 158 (0.4 percent). Of these 0.26 percent or 105 of 39,908 were repeatedly reactive. Eight hundred and sixty-seven cancer patients were also tested for HTLV antibodies. Eight or 0.9 percent were repeatedly reactive for HTLV antibodies by enzyme immunoassays (EIA), but only one could be confirmed as positive. HTLV-I/II has a very low incidence in the ambulatory population. The relationship of clinical sequelae and the rate of transmission of these viruses remain unclear. A readily applicable confirmatory test is not yet available. Even significant improvements in the sensitivity and specificity of testing will present ongoing problems for identification of true HTLV carriers. The clinical decision-making process related to the meaning of these results continues to be difficult.