Neonatal treatment of C3H mice (H-2k) with anti-Kk monoclonal antibodies results in altered cytotoxic responses against allogeneic targets. After 2-3 weeks of antibody treatment, no difference in the number of CD4+8- or CD4-8+ T cells was observed between the antibody- and saline-treated mice. However, antibody-treated mice had a significantly reduced cytotoxic response against various allogeneic major histocompatibility complex (MHC) class I-expressing targets. The strongest reduction was observed in very young mice (up to 2 weeks of age). As the mice got older, the allo MHC-specific responses reached control levels. No significant changes in T-cell receptor (TCR)-V-region usage was observed even in young antibody-treated mice. The results suggest that the reduction in the number of positively selecting elements reduces alloreactivity and most likely also the diversity of TCR-repertoire. However, the reduced alloresponsiveness was not restricted to either allogeneic K- or D-encoded molecules, suggesting that self MHC-D-region encoded molecules can mediate positive selection of T cells able to react against both K and D region-encoded allogeneic MHC class I molecules.