Seroepidemiological, clinical, immunological, and pathological features were studied in 315 intravenous drug abusers (IVDA) seen in five centers for drug addicts' assistance in the Friuli Venezia-Giulia region of Italy, close to the borders of Austria and Yugoslavia. No case of AIDS has been observed. Sixty-five (21%) were affected by persistent generalized lymphadenopathy (PGL). HTLV-III seropositivity was noted in 86 (27%) of the overall 315 IVDA, in 50 (77%) of 65 patients with PGL, and in 1 (0.5%) of 205 blood donors tested as a control group. Patients with PGL had a significantly lower OKT4/OKT8 ratio than the rest of the IVDA population and controls. Systemic symptoms were present in 52% of the patients with PGL, the most frequent symptoms being fatigue and night sweats. In 20 patients with PGL, DR typing revealed a significant increase in DR-5 frequency and a significant decrease of DR-2 frequency. The predominant histological features in the lymph nodes taken from 25 patients consisted of an exuberant follicular hyperplasia, capillary vessel proliferation, and plasmacytosis. Nineteen (22%) females reporting occasional prostitution were compared to 10 non-IVDA female prostitutes and concomitantly evaluated. HTLV-III seropositivity was noted in 11 (58%) of 19 IVDA female prostitutes and in none of the 10 non-IVDA prostitutes. Thirty-five couples composed of both IVDA were compared to 24 couples composed of an IVDA and a non-IVDA. Among the 24 couples of whom one or both partners were seropositive, concordance in HTLV-III seropositivity was present in 5/11 (45%) couples composed of both IVDA, and in only 1/13 (8%) couples composed of an IVDA and a non-IVDA. This suggests that the sharing of contaminated needles, universally practiced by our IVDA population, plays a more important role in the transmission of HTLV-III than sexual contact.