Among the cell surface antigens that can elicit an immune response in transplant recipients MICA antigens occupy a special place. They are similar to human leukocyte antigens (HLAs) while being very different from them. They are not as polymorphic and their quantity is smaller. In consequence, the impact of MICA antigens in transplantation is not as dramatic. However, our early guess that these ligands of NKG2D could elicit antibodies and cell-mediated immunity has been definitely confirmed. Careful analysis with MICA transfectant cells, for absorption and elution, established the specificity of the epitopes involved. Typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. Acute graft-versus-host disease was observed in stem cell recipients who were mismatched for MICA.