The development of serum and nasopharyngeal antibody responses to varicella-zoster virus (VZV) was studied in groups of children after naturally acquired varicella or after immunization with the Oka strain of live attenuated VZV vaccine administered in varying doses via respiratory inhalation or subcutaneous injection. Natural infection, subcutaneous immunization, and respiratory inhalation of large doses of VZV vaccine consistently resulted in the development of VZV-specific IgG antibody responses in serum. Although the serum IgG antibody responses persisted for at least eight to 12 months (to date) after either form of infection, the antibody activity appeared to be four- to eight-fold higher after natural infection than after immunization. Transient IgG antibody responses were observed in serum after respiratory inhalation of smaller doses of VZV vaccine. Natural infection, but not VZV vaccine, was associated with the development of serum and nasopharyngeal IgA responses to VZV in most subjects.