We have performed lymphocyte phenotypic analysis on serial lymph node biopsies and peripheral blood samples from 11 patients with the persistent generalized lymphadenopathy (PGL) syndrome and correlated the findings with histologic and clinical findings (median follow-up 18 months) in a search for factors that may predict evolution to acquired immunodeficiency syndrome (AIDS). Follow-up lymph node biopsies showed higher percentages of T-cells, both OKT4+ and OKT8+ phenotypes, and lower percentages of Slg+ B-cells and OKla+ cells. The lymph node changes were relatively minor in degree compared to the progressive peripheral blood OKT4+ lymphocytopenia observed over a similar time interval. The one patient who developed a malignant lymphoma had a high percentage of nodal T-cells and low peripheral blood T-cell counts. We conclude that serial lymph node studies contribute to an understanding of the natural history of PGL, but that peripheral blood counts are a more sensitive indicator of immune status in individual patients.