The lysability of Twelve human colorectal cancer cell lines maintained in long term culture, RAJI cells and K 562 cells were stidied. Three different donors of peripheral blood lympocytes (PBL) were repeatedly tested so that the cytotoxictty toward naturalkiller (NK), lymphokine activated killer (LAK), and the colon cancer targets could be compared and contrasted. NK cells were prepared from fresh PBL and the xytotoxicity in a Cr release assay determined. LAK cells from the same donor were generated by cultere in 10% conditioned media; the cultures with IL-2 were intiated three days earlier so that NK and KAK cytotoxicity were determined simultaneously. PBL from all three donors repeatedly showed lysis of K562. Also, for all three donors, lysis of K562 was increased using LAK cells. RAJI cells were lysed by NK in only four of twelve experminmts; yet, with LAK cells, RAJI was lysed in eight os twelve experiments. In all but four instance,s incubation with IL-2 increased RAJI lysis. Colon cancer cell lines, SNU-C5 and SNU-C2A, H684, H548 behaved as RAJI in that these tumor cells were not lysed by NK and the level of cytolysis. Lines H508,SNUC1, SNUC4, and H498 were not lused despite destruction of positive controls in the same experimet. LAK lyses of the colon cancer cell lines was consistent for all three donors bur NK lysis was yntredictable. Patterns of cell lysis for colon cancer lines were observed and some cess lines found to be resistent to both NK and LAK lysis. HLA-FR expression ysing immunoperoxidase on tumor cells did not correlate woth cytolysis.