In a series of 123 renal transplants performed in the presence of a positive crossmatch (either peak positive-current positive or peak positive—current negative), we have analyzed the immunoglobulin class and specificity of the donor-reactive antibodies. The immunoglobulin class was determined by dithiothreitol reduction and the specificity by cytotoxicity inhibition using mono-morphic antibodies specific for HLA class I, DR, and DQ antigens. There was good primary graft and regraft survival in the presence of peak positive and current positive crossmatches due to IgM non-HLA antibodies.There was also acceptable primary graft and regraft survival with peak positive—current negative cross-matches due to T and B cell IgM HLA class I antibodies, but not with IgG HLA class I antibodies. Positive B cell crossmatches due to IgM or IgG HLA antibodies were associated with good primary graft survival but poor regraft survival.