Lymphocyte homeostasis is regulated by proliferation of antigen-responsive T-cells in the peripheral circulation and their apoptosis. Patients with cancer have altered lymphocyte homeostasis. Spontaneous apoptosis of circulating CD8(+) antigen-responding effector T-cells contributes to rapid lymphocyte turnover and depressed absolute numbers of T-cell subsets observed in patients with cancer. A rapid transit of naive CD8(+) T-cells to the expanded memory pool and enhanced apoptosis of antitumor effector T-cells in the peripheral circulation of patients with cancer are partly responsible for this rapid lymphocyte turnover. Future strategies for restoration of normal lymphocyte homeostasis in cancer will involve therapies with survival cytokines and factors selected for extending survival of antitumor effector cells and establishing long-term immunologic memory.