The activity of polyamine oxidase down-regulates IL-2 production in cultures of peripheral blood mononuclear cells. Monocytes are the main source of this enzymatic activity which generates ammonia. We therefore assessed the production of ammonia by human monocytes. We report that human peripheral blood monocytes produce and secrete ammonia and that this activity peaks after 2 days of incubation in vitro. Ammonia production can be suppressed by inhibiting polyamine biosynthesis and polyamine oxidation; thus, the activity of polyamine oxidase in human monocytes generates ammonia. Ammonia production could serve as a measure of polyamine oxidase activity in human monocytes. The levels of ammonia produced in our system reduce human lymphocyte viability. Therefore, ammonia can be added to the list of macrophage products having cytotoxic and immunosuppressive potential.