Abstract Platelet aggregation in plasma from subjects with sickle cell anemia, not in crisis, was tested using the aggregometer. Aggregation induced by adenosine diphosphate (ADP), epinephrine, or collagen was decreased in platelet-rich plasma (PRP) from these subjects. Aggregation induced by ristocetin (1.09 mg/ml final conc.) was absent or was preceded by a lag phase in sickle cell PRP but not in normal PRP. Washed platelets from subjects with sickle cell anemia mixed with normal platelet-poor plasma (PPP) showed normal ristocetin-induced aggregation. Washed normal platelets mixed with sickle cell PPP showed progressive inhibition of ristocetin aggregation with increasing amounts of plasma. Dilution of the sickle cell PPP or increasing the final concentration of ristocetin to 2.4 mg/ml resulted in normal aggregation. Factor VIII antigen levels (196±16% S.E.M.) and factor VIII procoagulant activity (286±82%) were elevated in sickle cell plasma. Fibrinogen levels (239±42 mg%) were normal or slightly decreased; no relationship to aggregation was seen. These results suggest that an abnormally high factor VIII antigen/von Willebrand factor activity ratio is present in sickle cell anemia. It is postulated that inhibition of ristocetin-induced platelet aggregation by sickle cell plasma is related to competition for available ristocetin.