In this study, we have examined the role cell surface carbohydrates play in the activation of macrophages to kill tumor cells as well as the effect removal of tumor cell surface fucose has on the susceptibility of the treated target cells to the cytotoxic macrophages. After incubation of human monocyte-derived macrophages with alpha-L-fucosidase, a glycosidase which splits terminal alpha-L-fucose from oligosaccharides, the macrophages were no longer able to respond to lipopolysaccharide (LPS). These experiments strongly suggest that alpha-L-fucose probably comprises an essential part of the macrophage membrane receptor for LPS. In another series of experiments tumor cells were treated with alpha-L-fucosidase prior to co-cultivation with macrophages to determine whether the presence of alpha-L-fucose on the tumor cell surface had any effect on macrophage mediated cytotoxicity. It was found that the MA-160 sensitive tumor target, after alpha-L-fucosidase treatment, became resistant to the effects of the cyto-toxic macrophages whereas the effect of the alpha-L-fucosidase treatment was blocked by addition of alpha-L-fucose to the incubation mixture.