The antifungal activities of monocytes and resident macrophages have been extensively studied. Macrophages from different species and different anatomic sites vary in their capacity to inhibit and kill fungi. For example, activated murine peritoneal macrophages have potent antifungal effects on C. neoformans. However, investigators have been mostly unsuccessful demonstrating antifungal activity of activated human macrophages. The L-arginine-dependent generation of nitric oxide by activated murine macrophages appears to be at least partly responsible for antifungal effects. Generation of microbicidal concentrations of nitric oxide has been difficult to demonstrate in human macrophages, which may help to explain why antifungal effects seen in mouse macrophages have not always been reproduced in human cells.