Biochemical and cytochemical analysis of Lewis lung tumor variants revealed that the low metastatic cells contained more galactose/N-acetylgalactosamine residues in a high-molecular-mass (15-20 kDa) mixed N- and O-glycan fraction than the highly metastatic ones. It was also found that the highly metastatic variant was less sensitive to macrophage cytotoxicity in vitro. The cytotoxicity against the low metastatic target cells was inhibited by asialofetuin (10-20 microM), and, to a small degree--and at much higher concentration--by lactose, while galactose and other monosaccharides were ineffective. We suppose that complex galactosylated tumor cell membrane glycans could play a role in the antitumoral cytotoxicity of macrophages.