NK cells may mediate effector functions other than target cell cytotoxicity. To explore such noncytotoxic effector mechanisms, we tested whether human PBL and purified NK (CD56+) cells might induce expression of tissue factor by cultured porcine aortic endothelial cells. Tissue factor is the major coagulation factor that binds to factor VIIa and initiates coagulation. The addition of freshly isolated NK cells but not T cells to endothelial cells resulted in the induction of tissue factor activity. NK-depleted (CD56-) effector cells did not induce tissue factor activity; however, the combination of CD56+ cells and NK-depleted cells induced tissue factor activity to the same extent as unseparated cells. PBL induced tissue factor mRNA in porcine endothelial cells and NK depletion resulted in a significant decrease of the induction. Induction of tissue factor activity in porcine endothelial cells by human NK cells required direct cell-to-cell contact, as transfer of supernatants from NK-endothelial cell cultures to secondary cultures did not induce tissue factor activity, and anti-LFA-1alpha Abs inhibited the induction of tissue factor activity. Induction of tissue factor activity in endothelial cells by NK cells may represent one of a variety of ways in which NK cells mediate noncytotoxic effects.