Pre-existing alloantibodies against the mismatched HLA-A and HLA-B antigens of the donor, when present in current sera, are believed to be detrimental to kidney graft survival. When these antibodies are present only in historical sera, their immunoglobulin class has reported to be important with respect to the expected graft survival, IgG antibodies being associated with poor graft prognosis and IgM with reasonable graft survival. In the present study, we have tested whether the immunoglobulin class of anti-HLA antibodies is reflected in the activation state of CTLs directed against these HLA antigens as measured by their in vitro resistance or sensitivity to CsA. The results indicate that the presence of IgG anti-HLA antibodies is associated with the presence of activated CTLs (CsA resistant), whereas in the case of IgM antibodies, mainly naive CTLs (CsA sensitive) are found. This observation may explain the different prognoses of historical positive crossmatches due to IgG versus IgM alloantibodies.