The contribution of anti-donor immunological responses in valve homograft degeneration remains a matter of debate. High-avidity cytotoxic T lymphocytes (CTL) are destructive cells present in the graft and peripheral blood during rejection of heart or corneal homografts. The kinetics of the CTL were studied in peripheral blood of 15 valve homograft recipients, using an in vitro functional assay. Significant increase of all donor-specific CTL among peripheral blood mononuclear cells was seen in 14/15 (93%) recipients from 3 months (p = 0.045) up to 12 months (p = 0.015) after homograft implantation. A more significant increase was seen in the CTL fraction with high avidity for donor antigens. The number and avidity of donor-specific CTL are increased after implantation of cryopreserved valve homografts; this increase may indicate cell-mediated destruction of valvular tissue.