The immunogenicity of an individual human leukocyte antigen (HLA) class I mismatch is different for the cellular and the humoral alloimmune responses. The consequence is that the same antigen can induce a strong antibody response and no cytotoxic T lymphocyte reactivity, but the reverse can occur also. Exact knowledge of the immunogenicity of an HLA mismatch for an individual patient can lead to a strategy of tailor-made HLA mismatching if no HLA identical donor is available. Depending on the clinical situation, one should select a donor with HLA mismatches according to the humoral or cellular mismatch algorithm.