CD8 is either an alphaalpha homodimer or an alphabeta heterodimer, although most peripheral CD8-lineage T cells express only the CD8alphabeta heterodimer. The physiological function of CD8beta was elucidated with mice that were chimeric for the homozygous disruption of the CD8beta gene. The CD8beta-/- T cells developed normally to CD4-CD8+ stage, but did not efficiently differentiate further, which resulted in few peripheral CD8+ T cells. The number of peripheral CD8+ T cells was restored by transfer of an exogenous CD8beta gene into CD8beta-deficient T cells. Thus, CD8beta is necessary for the maturation of CD8+ T cells.