Humoral and cell-mediated immune responses to varicella-zoster virus (VZV) have been evaluated after 1 and 2 doses of live attenuated varicella vaccine, Oka strain, in several studies. One dose of varicella vaccine, however, elicits detectable immune responses that are low and, in some cases, may be insufficient for complete protection against the virus after the normal decline in humoral and cell-mediated immunity with time. In contrast, immune responses after 2 doses are significantly higher and approximate the levels seen after natural disease. These investigations of vaccine-induced immunity suggest that 2 doses of VZV vaccine will better achieve the goals of the VZV vaccination program, by reducing the VZV burden of disease in childhood and preventing accumulation of young adults who are susceptible to or only partially protected from varicella.