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Pentachlorophenol (PCP) is an organochlorine pesticide that decreases the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. They bind to these targets, utilizing a variety of cell-surface proteins. This study examined concentrations of PCP that decrease lytic function for alteration of NK binding to tumor targets. Levels of PCP that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. Exposure to 10 µm PCP for 24 h (which caused a greater than 70% loss of lytic function) decreased NK binding function (34.6%), and CD11a (21.7%) and CD56 (26.2%) cell-surface proteins. Both binding function and cell-surface proteins were decreased after longer exposures to lower concentrations of PCP. These data indicate that continuous exposures to PCP decreased binding function as well as cell-surface marker expression in NK cells and that these changes may in part explain the losses of lytic function seen with these exposures. PCP exposures have been shown to increase the incidence of blood and kidney cancers in humans. These data indicate that a possible explanation for this increased risk may be loss of NK lytic function, which is at least in part owing to the loss of the ability of the NK cell to bind to tumor cells. These data also indicate that lost binding function may be due to loss of important cell-surface proteins.