Apoptosis, or the ability of cells to die in an orderly and highly regulated manner, is essential for normal development and homeostasis of multicellular organisms. Diseases in which deregulation of this process is implicated include autoimmune diseases, cancer and Alzheimer's disease. The importance of apoptosis for the development and function of lymphoid cells has been extensively investigated. Less clear is the role apoptosis plays in regulating early progenitor and stem cell compartments. This question is being investigated using a transgenic mouse model, H2K-BCL-2, in which all hematopoietic cells have an increased resistance to apoptosis. The same transgenic model is also being used to address the question whether protection against apoptosis can increase system-wide resistance to lethal challenges such as irradiation and chemotherapeutic agents.