Two multiply transfused group O patients developed refractoriness to random-donor platelet transfusions. Both had high-titer IgG antibodies to group A and B antigens. Subsequent transfusions with ABO-compatible platelets were successful, suggesting that the ABO blood group system is significant in the development of refractoriness to platelet transfusions. By indirect immunofluorescence, the patients' IgG anti-A reacted with platelets from group A1 donors but not with those from group A2 donors. A2 platelets were at least 38 times less efficient at adsorbing a mouse monoclonal anti-A; the difference between the adsorbence capacities of A2 and O platelets was minimal. Transfusion of A2 platelets, unlike that of A1 platelets, effected a good increment in the platelet counts of these two patients. The results indicate that the expression of A2 antigen on platelets from A2 subjects is minimal.