Viral infections may induce an acquired form of immunodeficiency, generally lasting a few weeks. In the more severe form, such as HIV infection, the immunodeficiency is permanent. Programmed death of T cells represents one of the mechanisms by which HIV determines the T cell functional impairment, finally resulting in the destruction of T cells. In this study, we evaluated whether an altered regulation of apoptosis was also implicated in the anergy associated with the common measles or varicella-zoster virus (VZV) infections in infancy. A spontaneous apoptosis of peripheral blood mononuclear cells was observed in children who had suffered from these infections as long as 6 mo after the acute disease. Apoptosis was demonstrated through analysis of cellular DNA content, morphologic evidence of cell nuclei shrinkage, and by analysis of DNA degradation. Stimulation of T cells through anti-CD4 MAb increased the number of apoptotic cells with a maximal effect 72 h after the stimulation. Our results suggest that apoptosis may account for the anergy that follows acute viral infections in infancy.