HLA-DR-identical North American individuals of Caucasian, black, and Asian Indian origin were tested in checkerboard mixed lymphocyte cultures (MLCs) and the distribution of negative (weak), intermediate, and positive (strong) MLC reactions was determined using the linear clustering analysis program. Overall, the data show that the frequency of weak MLC reactions is significantly higher when the HLA-DR-identical responderstimulator pair derives from the same ethnic group than when they are of different ethnic origin. Caucasians responded stronger to blacks than to Asian Indians; blacks responded stronger to Asian Indians than to Caucasians, while Asian Indians responded stronger to blacks than to Caucasians.The fact that the frequency of MLC identity is greater among HLA-DR-identical individuals of similar as opposed to different ethnic origin suggets that the predictability of successful transplants by HLA-DR matching may be also influenced by the ethnic background of the donor.