To determine the potential role of immune dysfunction in feline immunodeficiency virus (FIV)-associated lymphomagenesis, we present the results of immunological monitoring during the chronic phase of experimental FIV infection in two cats which subsequently developed lymphoma. In one cat, C1, cell-mediated immunity was depressed throughout the monitoring period but particularly from 125-200 weeks post-infection (pi), when this cat demonstrated profoundly impaired lymphocyte blastogenesis and markedly increased interleukin-1 (IL-1) production compared to age-matched, uninfected control cats. Lymphocyte function in the other cat, C2, was preserved to a greater degree. Alterations in the levels of immunoglobulin isotypes M, A and G in CD4+-, CD8+- and CD21+-lymphocyte sub-sets were demonstrated in both cats. Southern blot analysis revealed the presence of integrated FIV-provirus in tumour DNA from C2 but not C1 indicating a possible direct role for the virus in the former case only. In this study we have characterised, for the first time, the FIV-induced immune dysfunction in cats which developed lymphoma, demonstrating potential indirect mechanisms of tumourigenesis.