l-arginine uptake systems in macrophages play a role in regulating nitric oxide synthesis via the inducible l-arginine nitric oxide pathway. This paper describes the association of l-arginine transport with nitric oxide production in human peripheral blood monocyte-derived macrophages and in peritoneal macrophages from control and inducible nitric oxide synthase knock out C57BL6 mice. Experiments performed with human macrophages suggested that little or no nitric oxide was produced in human macrophages in vitro and that human macrophages exhibit a different arginine transport-specific response to stimuli compared with rodent macrophages. We conclude that increased l-arginine transport in both human and murine macrophages is dependent on the requirement for intracellular nitric oxide.