In the present study we have evaluated the histological, immunohistochemical, ultrastructural and cell surface phenotypic features of lymph nodes from 19 intravenous drug abusers and two homosexual men with persistent lymphadenopathy syndrome and from six control patients. Our investigation has demonstrated that the lymphadenopathy of drug abusers is characterized by: (a) specific histological features with evidence of evolution from an initial hyperplastic-reactive to a late regressive-destructive stage; (b) T-cell surface phenotype distribution similar to that in the peripheral blood of homosexuals; (c) peculiar infiltration of the germinal centres by T8+ cells and by S-100+, T6+ interdigitating reticulum-like cells; (d) electron microscopic features indicating the presence of virus bodies in lymph node cells and in the intercellular spaces. These data suggest that the lymphadenopathy of drug abusers and homosexuals are similar pathological conditions with characteristic features which allow histological differentiation of this entity from those found in other viral infections.