Tumor necrosis factor alpha (TNF-alpha) signaling gives rise to a number of events, including activation of transcription factor NF-kappa B and programmed cell death (apoptosis). Previous studies of TNF-alpha signaling have suggested that these two events occur independently. The sensitivity and kinetics of TNF-alpha-induced apoptosis are shown to be enhanced in a number of cell types expressing a dominant-negative I kappa B alpha (I kappa B alpha M). These findings suggest that a negative feedback mechanism results from TNF-alpha signaling in which NF-kappa B activation suppresses the signals for cell death.