Viral particles have been demonstrated by electron microscopy in lymph nodes from patients with acquired immune deficiency syndrome AIDS-related persistent generalized lymphadenopathy (PGL) syndrome. Immunohistochemical and in situ hybridization studies have identified these viruses as the human immunodeficiency virus (HIV). In this study, we examined 20 PGL lymph nodes and found viral particles in 18 cases. Immunohistochemical studies on these cases revealed positive staining for the HIV core protein P24 within germinal centers of secondary follicles. In addition we found viral particles, morphologically indistinguishable from those observed in PGL lymph nodes, in 13 of 15 non-HIV related reactive lymph nodes. Immunohistochemical staining of these lymph nodes for the P24 core protein was negative. None of the patients in this group had risk factors for developing AIDS and none exhibited clinical evidence of immune deficiency. We conclude that the viral particles observed in PGL lymph nodes are most likely HIV, but similar particles can be seen in reactive lymph nodes not associated with HIV infection. The discrete localization of these particles within germinal centers has been observed for other viruses and immune complexes and a possible mechanism of this antigen deposition is discussed.