To examine the effect of extracorporeal membrane oxygenation (ECMO) therapy on platelet function and number and to determine the in vivo survival of transfused platelets during ECMO. Prospective study of all neonates treated with ECMO during a 6-month period. Neonatal intensive care unit in a tertiary referral center. Ten infants, < 1 wk of age, with respiratory failure requiring ECMO. None. Platelet counts were measured at timed intervals to determine the effect of ECMO on platelet counts. The change in platelet counts after transfusion was also measured. Whole blood platelet aggregation studies were performed to determine the effect of ECMO on platelet function. A mean decrease of 26% from the baseline platelet count was found 15 mins after the initiation of ECMO, with an additional mean decrease of 16% by the end of 1 hr (p < .05). Fifteen minutes after platelet transfusions, a 17% mean increase in platelet counts was measured (p < .05). One hour after platelet transfusion, the platelet count had decreased to pretransfusion values. Platelet aggregation studies 15 mins after starting ECMO showed a 46% mean decrease in the response to collagen from baseline (p > .05), and a significantly (p < .05) reduced response to ristocetin and to adenosine 5'-diphosphate. Platelet adenosine triphosphate release was also significantly reduced. Single-unit platelet transfusions failed to correct platelet aggregation abnormalities. Resolution of platelet aggregation abnormalities and normalization of platelet counts occurred 8 hrs off ECMO. The results of these studies show that qualitative and quantitative platelet changes occur while a neonate is receiving ECMO. The survival rate of transfused platelets is reduced, and the acquired platelet dysfunction is not reversed by the transfusion of platelets with normal function while the patient is receiving ECMO.