Human Natural Killer (NK) cell activity against K562 target cells has previously been shown to be inhibited by certain monosaccharides and glycoproteins in a specific fashion. Glycopeptides have been prepared from the isolated plasma membranes of cultured K562 cells by extensive pronase digestion and fractionated by lectin affinity chromatography. Nine different fractions were tested for their ability to block 51Cr release by K562 targets in the presence of NK cells; two of the fractions, one isolated on RCA I lectin and the second on Pea lectin, were very effective at blocking cytotoxicity (greater than 80% inhibition) while the other fractions were only marginally effective. Furthermore, evidence is presented which demonstrates the blocking activity of the glycopeptides occurred at a lytic rather than a recognition step.