The available information provides a potential link between the developing dysfunction seen in immune cells obtained from septic animals and suggests ways in which these changes may be related to the expression of various pro- and/or anti-inflammatory mediators released during sepsis. While not mutually exclusive, we hypothesize that the developing immune response might be affected at several points, of which induction of cell death via apoptosis might be a result (see Figure 5). Possible hypothetical steps at which the development of a competent host immune response to bacterial challenge associated with polymicrobial sepsis might be inhibited are: 1) direct inhibition of the activation/differentiation of immune cells produced by the action of immune suppressive agent(s) which do not lead to the induction of cell death via apoptosis; 2) indirect inhibition of the activation/differentiation of immune cells (due to their loss), produced by the overt induction of cell death via apoptosis by mediator(s); 3) direct/indirect inhibition of the activation/differentiation of immune cells (due to their loss), produced by the induction of cell death via apoptosis due to loss or removal of specific growth factor(s); and/or 4) incomplete antigenic stimulation due to lack of co-stimulatory signal, etc., and/or superantigen (e.g., exotoxin) overstimulation leading to overt activation induced programmed cell death. As alluded to above, the process of apoptosis associated with the development of an apoptotic state is irreversible once a cell has progressed through the F-phase. Thus, it has become important to be able to assess the state of the cells or tissue/organs with respect to the extent to which the cells are undergoing apoptosis. In conclusion, while we have hopefully begun to shed some light on the process apoptosis, with respect to the septic animals lymphoid system much still needs to be understood about how and why cells of the immune system undergo programmed cell death and its significance to the developing immune dysfunction associated with polymicrobial sepsis.