The authors have examined two separate series of samples from 33 and 23 anti-HIV positive patients with persistent generalized lymphadenopathy (PGL) undergoing lymphnode biopsy. For the first group of patients, the aim was to evaluate the diagnostic and prognostic correlation between clinical and laboratory features and histologic findings. For the second group, an assessment was made of the indications for lymphnode biopsy as determined by the rate of positive histopathologic findings. Histologic alterations were classified into four types according to Ràcz, without knowledge of clinical and laboratory data. At the time of biopsy, the first sample (n = 33) included 21 lymphadenopathy associated syndrome (LAS) (64%), 6 ARC (18%), and 6 AIDS (18%) patients; a significant prevalence of type 1 histologic features was evident in LAS/ARC patients, while type 4 was exclusively present in the AIDS group. These preliminary results suggested that only symptomatic anti-HIV positive patients (ARC/AIDS) should have been selected for lymphnode biopsy, because of the expected high rate of opportunistic infections, malignant lymphoma, or Kaposi's sarcoma (KS) in this specific subset of patients. Actually, in the second sample of 23 patients (ARC = 8: AIDS = 15) the detection rate of AIDS-related neoplasms included ten Kaposi's sarcoma and three Hodgkin's disease. These findings suggest that diagnostic lymphnode biopsies should be limited to selected anti-HIV positive patients with evidence of AIDS-related neoplasms or treatable opportunistic infections, or for the purpose of detecting histopathologic features of prognostic significance.