NK cells can recognize and lyse target cells without restriction by the MHC. The molecular interaction responsible for NK cell recognition is poorly understood. It has been frequently suggested that the loss of beta 2 integrin in immune competent cells may lead to dysfunction due to inadequate cell-cell interaction. We examined the role of lymphocyte functional adhesion molecule-1 in the function of a human natural killer leukemia cell line, YT-1. A mutant YT-1(-) cell subclone showed an absence of killing activity against a B lymphoma cell line, compared with that against a CD11a/CD18 positive parental cell line, YT-1(+) cells. We found that this loss of cytotoxicity was correlated with lack of surface expression of CD11a/CD18 molecules due to the mutation of the CD18 gene. Using gene transfer experiments, we provide strong evidence demonstrating that CD18 transfection to this mutant NK cell line, YT-1(-), restored the surface expression of CD11a/CD18, and this restoration was accompanied by reexpression of cytotoxic function.