The size and composition of the CD4⁺ T-cell population is regulated by balanced proliferation of progenitor cells and death of mature progeny. After infection with the human immunodeficiency virus, this homeostasis is often disturbed and CD4⁺ T cells are instead depleted. Such depletion cannot result simply from accelerated destruction of mature CD4⁺ T cells — sources of T-cell production must also fail. Ironically, this failure may be precipitated by physiological mechanisms designed to maintain homeostasis in the face of accelerated T-cell loss.