The existence of structures on NK-sensitive target cells selectively recognized by the effector cells have been postulated. To test this hypothesis, four selected human cell lines were investigated for target-cell proteins which could serve as specific ligands for the putative NK-cell receptor(s). NP-40 extracts from two highly NK-sensitive (K 562 and Molt-4) and two rather insensitive cell lines (HL-60 and Reh-6) were fractionated on SDS-polyacrylamide gels and tested for their ability to inhibit binding of effector to target cells as well as NK cytotoxicity. Three fractions with molecular weights (MW) of 200, 120 and 80 +/- 10 KD isolated from K 562 cells were able to inhibit binding of large granular lymphocytes (LGL) to K 562. Of the other cell lines, Molt-4 and HL-60, both which were able to inhibit lysis of K 562 in a cold target inhibition assay, showed also two inhibitory fractions with MW 120 and 80 KD, whereas Reh-6, which is not able to compete with 51Cr-labelled K 562 in a cytotoxicity assay, lacked these structures. The 200, 120 and 80 KD fractions isolated from K 562 and the 120 and 80 KD fractions from Molt-4 and HL-60 were able to inhibit lysis of K 562 cells when added to the cytotoxicity assay. By adsorption/elution of radiolabelled K 562 extracts to/from LGL it was possible to detect an 80 KD target-cell surface protein which became preferentially bound by LGL-enriched but not by LGL-depleted lymphocyte preparations. Our results indicate the existence of target-cell proteins in NK-sensitive cell lines which serve as specific ligands for binding of NK cells. These target-cell structures of human cell lines differed from NK target structures described for mouse-NK-sensitive cell lines.