Humoral and cellular immune responses to whole varicella–zoster virus (VZV) antigen and to the VZV glycoprotein I (gpI) and immediate early protein (IE–62) were compared in two populations of healthy children who received different lots of the Oka/Merck varicella vaccine. Children who were given vaccine containing 950 pfu with a relative antigen content of1.0 (lot C–K472) per dose, in an earlier protocol, had an initial seroconversion rate of87% but VZV cell–mediated immunity was diminished at 8 weeks and 1 year after immunization. At 1 year, the percentage ofvaccinees with T lymphocyte proliferation to whole VZV, gpI, or IE–62 was 98%, 77%, and 83% for recipients of the 1140 pfu/l.7 relative antigen or 1145 pfu/l.6 relative antigen content vaccines compared with 43%, 40%, and 40% among those given the vaccine with 950 pfu/1.0 relative antigen content. Since the more immunogenic vaccines contained 1.5–2.0 times more viral antigen and only 20% more infectious virus, viral antigen content may affect the immunogenicity of the varicella vaccine, particularly as reftecteJ in the cell–mediated immune response. The current vaccine preparations elicited cellular and humoral immune responses to whole VZV antigen and memory T lymphocytes specific for major viral proteins that were detectable 1 year after immunization. © 1990, by The University of Chicago.