In addition to self tolerance, the immune system needs to be regulated when a response has been initiated. Recent data suggest that activated T and B cells, as well as immature lymphocytes, are susceptible to programmed cell death and that Fas:Fas ligand (FasL) interactions play an important role in this process. However, while T cells may kill themselves via a Fas-dependent pathway, we propose that B cells undergo activation-induced apoptosis independent of Fas, yet can be susceptible to T cell-mediated, FasL-induced death. Therefore, T cells can 'commit suicide, but B cells are 'murdered' during the regulation of an immune response! Further evidence is presented to support the hypothesis that T cell and B cell apoptosis are initiated through fundamentally different pathways.