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 of 1.0 (lot C-K472) per dose, in an earlier protocol, had an initial seroconversion rate of 87% but VZV cell-mediated immunity was diminished at 8 weeks and 1 year after immunization. At 1 year, the percentage of vaccinees with T lymphocyte proliferation to whole VZV, gpI, or IE-62 was 98%, 77%, and 83% for recipients of the 1140 pfu/1.7 relative antigen or 1145 pfu/1.6 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 reflected 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.