We have recently shown that leukotriene B4 (LTB4) activates T lymphocytes to become suppressor cells. We now report that LTB4 also augments human natural cytotoxic cell activity against target cells infected with herpes simplex virus. This activity is partially inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid and the thromboxane synthetase inhibitor OKY-1581, but is augmented by indomethacin. We suggest that LTB4 may play a role in early host defense responses during inflammatory and infectious disease processes.