The normal immune response after primary varicella-zoster virus (VZV) infection includes IgG subclass evolution to predominantly IgG1-type antibodies, and maturation from low to high avidity antibodies which are maintained for life. Twenty-three healthy and apparently immunocompetent children with a history of 2-5 episodes of chickenpox were studied after repeat disease. Serial sera were tested for VZV-IgG subclass patterns and VZV IgG and G-subclass antibody avidity by urea elution enzyme linked immunoassay (ELISA). Of 11 patients studied within 8 weeks of repeat chickenpox (Early Group), mean antibody avidity was significantly lower (31.3 +/- 26.81) than control (65.1 +/- 12.38) (P < .001). Seven had low avidity antibody (< 30 percent) and an abundance of IgG3 which was a pattern like primary chickenpox, and 2/11 had high avidity antibody characteristic of anamnestic responses. Early Group patients and 12 others studied over 8 weeks after repeat disease (Late Group) showed avidity maturation and attrition of IgG subclass antibodies other than IgG1. At least nine children failed to show VZV-specific secondary (memory) immune responses early in the course of repeat disease. It is possible that failure to maintain or evoke a secondary immune response could explain their susceptibility to repeat chickenpox.