The incidence and characteristics of HLA alloimmunization following transfusions of leukocyte concentrates as a source of enzyme replacement were determined in male patients with Hunter's syndrome. Five patients were given leukocyte concentrates from HLA matched donors (Group I) and another five patients received leukocyte concentrates from non-HLA matched donors (Group II). No other blood products were transfused in either group. Immune response pattern of HLA alloimmunization measured as the proportion of screening cells manifesting cytotoxicity with patient's sera obtained during the follow-up period was similar in both groups. HLA alloimmunization is seen with transfused leukocyte concentrates from either HLA-matched or non-HLA-matched donors in patients with Hunter's syndrome. There appears to be a trend for an earlier onset of HLA alloimmunization with fewer transfusions when leukocyte concentrates from non-HLA-matched donors are transfused as compared to leukocyte concentrates from HLA-matched donors. Once HLA alloimmunization occurs, immune response patterns appear similar with either leukocyte product.