In theory, the potency of cryoprecipitated antihemophilic factor (cryo) can be increased by utilizing plasma only from donors with high levels of factor VIII procoagulant activity (fVIIIc). Previous reports have suggested that plasma of group O individuals has, on the average, less fVIIIc than plasma from individuals of blood groups A, B, and AB. We have investigated the feasibility of increasing the potency of cryo by preselecting plasma for cryo production on the basis of the blood group of the donor. FVIIIc levels of fresh plasma, fresh frozen plasma (FFP), and cryo (prepared both by air-thaw and water-thaw methods) were assayed. The plasma, FFP, and cryo from group O donors contained only 75% of the fVIIIc present in plasma from group A, group B, and group AB donors. Following infusion to patients with hemophilia, in vivo recovery and survival of fVIIIc activity from groups A, B, and AB cryo reflected the higher in vitro levels. The mean potency of bags of cryo can be increased, and the cost of hemophilia treatment with cryo can be reduced by excluding group O plasma from the production of cryoprecipitate.