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Human natural killer (NK) cells are lymphocytes that destroy tumor cells, virally-infected cells, and antibody-coated cells. Tetrabromobisphenol A (TBBPA) is used both as a reactive and as an additive flame retardant in a variety of materials and appears to contaminate the environment. TBBPA has been found in human blood samples and if it interferes with NK cell function, this could increase the risk of tumor development and/or viral infection. The present study examines the effects of exposure to various concentrations of TBBPA for 24 hr, 48 hr, and 6 days on the lytic function, tumor-target-binding function, and ATP levels of NK cells. These same parameters were also monitored in NK cells that were exposed to TBBPA for 1 h followed by 24 hr, 48 hr, and 6 days in TBBPA-free media. A 24-h exposure of NK cells to 5 μM TBBPA caused a >95% decrease in NK lytic function, a 70% decrease in binding function, and a 34% decrease in ATP levels in NK cells. Exposure to 2.5 μM TBBPA for 24 h decreased lytic function by 76%, binding function by 20%, and had no effect on ATP levels. Exposure of NK cells to 5 μM TBBPA for 1 h followed by 24 h in TBBPA-free media caused a progressive and persistent loss of lytic function (41%) while not affecting either binding ability or ATP levels. The results indicate that TBBPA exposures decrease the lytic function of human NK cells and that an initial brief (1 hr) exposure can cause a progressive loss of function. In addition, the data also indicate that TBBPA-induced loss of NK lytic function can occur at a concentration of TBBPA that does not affect target-binding ability and ATP levels of NK cells.