An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I--associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.