Immunohistologic analysis of cellular changes in serial lymph node biopsies of eight patients with persistent generalized lymphadenopathy (PGL) syndrome was performed and correlated with clinical and laboratory findings to better determine the natural history of human immunodeficiency virus (HIV) infection. The authors observed decreased follicle size and area in the second biopsies of six of the eight patients, associated in some with increased numbers of B-cells in medullary regions (four of eight) and more involuted follicles (four of eight). Five cases showed progressively increased paracortical areas in the second biopsies, with increased numbers of T-cytotoxic/suppressor cells and decreased T-helper cells. Seven of the patients also had a progressive loss of T-helper cells in the peripheral blood. These findings provide tissue and peripheral blood evidence for progressive immunologic deterioration in some patients with PGL.