The human T-cell antigen receptor (TcR) V beta repertoire was investigated following in vivo reimmunization with tetanus toxoid (TT). Four healthy subjects were immunized subcutaneously with TT, and 24 samples of peripheral blood T cells were taken at intervals over several weeks and used to generate TcR-C beta chain-specific first-strand cDNA. A semi-quantitative assay utilizing the polymerase chain reaction (PCR) was used to measure the amount of 22 different TcR-V beta gene transcripts in the cDNA. A peak increase in the amount of V beta 2, 4, 6, 13.1 and 14 occurred 14 days post-immunization, with each V beta increased in at least two of the four subjects. No obvious changes in the other 17 V beta genes were found. A secondary antibody response to TT occurred in all subjects by day 14. These results show that it is now possible to characterize the in vivo kinetics of the human TcR repertoire following stimulation with a conventional antigen.