We studied a 58-year-old black woman from Barbados who simultaneously developed myelopathy and lymphoma with human T-lymphotropic virus type I (HTLV-I) antibodies in serum and cerebrospinal fluid and died 3 years after onset. Neuropathological examination showed typical tropical spastic paraparesis (TSP). The polymerase chain reaction (PCR) demonstrated defective proviral genome retaining the HTLV-I pX and env regions in thoracic spinal cord, the level most severely affected. Defective HTLV-I in the nervous system retaining the pX region may be relevant to pathogenesis because circulating CD8+ cytotoxic lymphocytes specific for HTLV-I pX occur in HTLV-I myelopathy. This patient's lymph node biopsy specimen was consistent with Hodgkin's disease (HD), nodular sclerosis subtype, of B-cell origin. The PCR in the paraffin-embedded lymph node involved by HD failed to amplify HTLV-I proviral sequences. Complete HTLV-I proviral amplification was obtained in paraffin-embedded lymph nodes form positive controls (adult T-cell leukemia). To our knowledge the association of TSP and HD has not been reported previously. Despite claims that HD may be associated with HTLV-I, we demonstrated absence of HTLV-I-infected T cells in the lymphoid infiltrate of HD in this case, positive HTLV-I serology notwithstanding.