Persistent generalized lymphadenopathy (PGL) is the most frequent AIDS related manifestation in homosexual men. From May 1984 to March 1985, 45 (38%) out of 117 intravenous (iv) drug abusers evaluated had PGL. Thirty-two were males and 13 females (median age 25 years). All patients referred to the frequent sharing of syringes. The median duration of lymphadenopathy was 3 months (range 3-60) with a median number of involved extrainguinal sites of 4 (range 2-7). Systemic symptoms and energy to skin tests were common, whereas splenomegaly and past infections were less frequently encountered. Hypergammaglobulinemia and an inverted T helper/suppressor ratio and lymphopenia were found in 78%, 43%, and 20% of the patients, respectively; the presence of HTLV-III antibodies was demonstrated in 12 (46%) of the 26 tested patients. Histologically, excised lymph nodes from 14 patients exhibited a marked follicular hyperplasia, diffuse plasmacytosis, and a conspicuous capillary proliferation. All patients are followed on a regular basis with clinical examination and laboratory tests; in no case has AIDS or a malignant lymphoma so far developed.