Fetomaternal incompatibility of platelet alloantigens may lead to alloimmunization and neonatal alloimmune thrombocytopenia (NAIT). Human platelet alloantigen (HPA) 6b, which associates with residue Gln 489 of platelet membrane glycoprotein IIIa, has been described as a cause of NAIT. We have studied the MHC genes of all available family members in the six thus far reported families with a thrombocytopenic newborn and fetomaternal HPA-6b incompatibility. Maternal HPA-6b antibodies could be detected in five mothers to the altogether seven thrombocytopenic male infants. The MHC genes HLA-DRB, -DQA1, -DQB1, -DPB1, TAP1,2 and HSP70-Hom were studied by using polymerase chain reaction (PCR)-based DNA analysis methods. All five mothers with detectable circulating HPA-6b antibodies at the time of delivery shared an identical DRB1*1501, DQA1*0102, DQB1*0602 haplotype. The sixth, HPA antibody negative mother and a HPA-6b-negative mother to a healthy HPA-6b+ child were negative for this haplotype. The frequency of DRB1*15-positive haplotype was increased in immunized mothers (100%) as compared with the general Finnish population (27%), but the association was not statistically significant after correction. We conclude that there is a potential association between the MHC haplotype DRB1*1501, DQA1*0102, DQB1*0602 and alloimmunization to the HPA-6b antigen and that this alloimmunization probably involves different HLA class II molecules from immunization to HPA-1a.