Twelve specific-pathogen-free (SPF) kittens aged 8-12 weeks were serially infected in pairs every 6 weeks, by the intraperitoneal route, with the feline immunodeficiency virus (FIV). Three additional SPF kittens were kept as controls. The infected animals were killed 10 weeks after inoculation, during the primary phase of the FIV infection. Generalized lymphadenopathy (GL) was observed in the first three pairs of cats. All lymph nodes examined from the 12 infected cats showed histological changes. These included severe follicular hyperplasia with hyperactive follicular centres (FCs) which were either (1) naked, (2) infiltrated by lymphocytes, (3) seen to contain islets of lymphocytic mantle cells, or (4) disrupted by lymphocytes. The presence of both CD4+ and CD8+ T lymphocytes was demonstrated in the FCs immunocytochemically. The distribution of CD4 lymphocytes resembled that in control lymph nodes, but the CD8 cells were increased in number and either scattered or clustered in the follicles. In addition, varying degrees of interfollicular proliferation and medullary plasmacytosis were observed in the lymph nodes. These findings, which were common to all infected animals, represented distinct prodromal manifestations of FIV infection. The changes in lymphocyte subpopulation distribution observed in early FIV infection were reminiscent of findings encountered in human immunodeficiency virus (HIV) infection and reinforce the suggestion that FIV infection is an appropriate model for the study of HIV pathogenesis