The purpose of this study is to compare the clinical and laboratory findings at presentation of 38 intravenous drug abusers with pathologically documented persistent generalized lymphadenopathy and 50 patients with biopsy proven malignant lymphoma (30 Hodgkin diseases, 20 non-Hodgkin's lymphomas) not related to acquired immunodeficiency syndrome, all aged 40 years or less and consecutively seen and evaluated with a similar clinicopathological approach since May 1984 in a single institution, Centro di Riferimento Oncologico, Aviano, Italy. Our results document that, although pathology is the decisive diagnostic tool, selected clinical and laboratory findings may contribute to a better differentiation of persistent generalized lymphadenopathy from malignant lymphoma not related to acquired immunodeficiency syndrome. Therefore, young patients presenting with generalized lymphadenopathy, apparently not related to known groups at risk for acquired immunodeficiency syndrome, should be evaluated also according to a protocol which includes the detection of symptoms, signs, and laboratory data that are known to be significantly increased among patients with persistent generalized lymphadenopathy.