Prevalence of lymphoproliferative disorders is increased in populations with various chemical exposures, including organophosphorus compounds. Lymphomas are also more common in individuals with a substantially decreased monocyte esterase activity. Organophosphorus compounds inhibit esterases associated with monocytes, natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytotoxic T lymphocytes, and these inhibitory effects impair immune surveillance and cytotoxic functions mediated by such cells. Lymphoma development is also associated with Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) infections, which are regulated by cytotoxic immune responses mediated by monocytes, T cells, and NK cells. My hypothesis is that lymphomagenesis is a multistep process, and the absence or inhibition of monocyte esterase and perhaps other immune cell esterases alters esterase-dependent detoxification of a factor critical for the early steps of oncogenesis. Also, such an enzyme deficit might impair the processes that regulate the dissemination and limit the total burden of pathogens such as the lymphoma-associated herpesviruses. An added risk to any viral-mediated lymphoproliferation might be an organophosphorus-induced oncogenic genetic change.