Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity of activated macrophages. Macrophages can be activated for tumor cell killing by microbial products, including lipopolysaccharide (LPS) and various cytokines. Here we report that in contrast to mouse macrophages, human peripheral blood monocytes stimulated with cytokines or LPS failed to release NO. Also priming of monocytes with interferon-gamma followed by activation with cytokines or LPS did not cause NO secretion. However, monocytes responded with NO production to stimulation with some human cancer cells but not with untransformed cells. NO production by monocytes was inhibited by NG-monomethyl-L-arginine, specific inhibitor of NO synthase and emetine, an irreversible blocker of protein synthesis. This may imply that human monocytes are unique in their restricted capacity to produce NO following interaction with some tumor cells, but not with other stimulators, and in this respect they may be able to distinguish between malignant and normal cells.