Two human retroviruses, HIV-1 and HTLV-I, have been associated with myelopathies in addition to other neurologic disorders. We report an American dually infected with HIV-1 and HTLV-I who developed steroid-responsive myeloneuropathy. This 28-year-old bisexual man developed interstitial pneumonitis and a transient midthoracic sensory level followed by the evolution of a slowly progressive spastic paraparesis and sensorimotor neuropathy. Serologic studies demonstrated coinfection with both HIV-1 and HTLV-I. Peripheral blood absolute CD4 count was persistently within the normal range. Cranial MRI was normal and spinal MRI showed T3-T10 atrophy. Serial CSF analyses demonstrated marked intrathecal synthesis of anti-HTLV-I IgG, lymphocytic pleocytosis, elevated protein and immunoglobulin G, and oligoclonal bands. HIV-1 was isolated from CSF but not from peripheral nerve. Lymphoproliferative studies confirmed spontaneous proliferation in both blood and CSF. Soluble interleukin 2 receptor and soluble CD8 were greatly elevated in blood and CSF when compared with patients with HIV-related vacuolar myelopathy and seronegative patients with other causes of myelopathy. Nerve biopsy showed epi- and endoneurial CD8+ lymphocytic infiltration without vasculitis; muscle biopsy showed features of acute and chronic denervation. A 6-week course of prednisone produced sustained improvement in leg strength and walking times. We speculate that the myeloneuropathy was caused by HTLV-I in the setting of coinfection with HIV-1.