The live varicella vaccine has been recommended for use in immunocompromised subjects and in adults who are susceptible to chickenpox. However, we do not know how humoral and cell-mediated immune responses induced after vaccination differed from those obtained after natural infection. To answer this, 45 previously infected subjects (23 chickenpox, 22 vaccinated) were tested for their varicella zoster virus (VZV)-specific antibody levels and for their lymphocyte stimulation responses to VZV antigen. Antibody was measured by both an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IF), while lymphocyte stimulation was detected by tritiated thymidine incorporation. Antibody was tested in ten postchickenpox and nine vaccinated subjects. About 6 to 8 weeks after first exposure, the magnitude of the responses determined by both ELISA and IFT were much higher in the naturally infected than in the vaccinated group (P less than 0.001) with both test methods). There was no significant difference in the lymphocyte transformation responses in both groups of subjects. Thirteen postchickenpox and 13 vaccinated subjects who had been infected at least 12 months previously were also tested. Total antibody levels were again significantly higher in the naturally infected than in the vaccinated group (P less than 0.001). One vaccinated subject had VZV-specific IgA and IgM in the serum. The magnitude of the lymphocyte transformation reaction was higher in the naturally infected than in the vaccinated group (P less than 0.01). Thus, antibody responses to VZV were better in naturally infected than in vaccinated subjects. The IFT appears to be a more sensitive technique for antibody detection in the vaccinated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)