Bovine leukemia virus belongs to a small subfamily of exogenous retroviruses that includes the human retroviruses HTLV-1, HTLV-II and the simian virus, STLV-1. Like other retroviruses, infection with BLV results in deregulation of the host immune system at both humoral and cellular levels. An approach which might help in the elucidation of some immune impairment phenomena is the investigation of the role that cytokines play in the pathogenesis and immune response of BLV infected animals. Here we describe our findings on IL-6 and TNF. We have found that the levels of IL-6 in the sera of BLV infected cows which show persistent lymphocytosis (BLV+ PL+) were significantly higher than those of BLV infected with no lymphocytosis (BLV+ PL-) or BLV negative cows (BLV-). The same results were obtained by measuring the spontaneous production of IL-6 in peripheral blood mononuclear cells (PBMC). Furthermore, PBMC derived from BLV+PL+ cows secrete higher levels of IL-6 and TNF alpha than those derived from BLV+PL- and BLV- ones following in vitro exposure to the BLV gp51 antigen, bacterial endotoxins (LPS) and ConA. Similar results were obtained when supernatants from stimulated adherent (monocytes, macrophages) and non-adherent cells (B and T lymphocytes) were tested. When exogenous IL-6 and TNF alpha were added to BLV infected cells in vitro, the expression of viral antigens was strongly suppressed. Thus, the possibility exists that the elevated production of IL-6 and even more than that of TNF alpha play a role as contributing factors to the latency of the clinical expression in BLV infection.