Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1.