Treatment with extracorporeal membrane oxygenation ECMO) is associated with side effects, e.g., blood cell consumption and activation. Our group has earlier shown that nitric oxide administered as a gas reduces platelet consumption and activation. In the present work we have studied the effect of the NO-donor S-nitroso-glutathione GSNO) on platelets and leukocytes in an in vitro extracorporeal circuit. Two complete ECMO circuits were perfused with fresh heparinized human blood for 24 hours. GSNO was administered as a continuous infusion to one circuit at a rate of 0.7 mg/hour in four paired experiments and at a rate of 3.5 mg/hour in another four paired experiments. The other circuit was used as a control. Blood samples were withdrawn from both circuits before the start of the experiments and at 0.5, 1, 3, 12, and 24 hours of perfusion. The samples were analyzed for red blood cell count, leukocyte count, platelet count, platelet membrane expression of glycoproteins GP) Ib and GPIIb/IIIa, leukocyte membrane expression of cluster of differentiation CD) 11b/CD18, as well as plasma concentration of tumor necrosis factor TNF)-alpha, interleukin IL)-1beta, and IL-8. No difference in these parameters between the GSNO and the control circuit at any time point was assayed. In this study, no significant effect of GSNO on circulating platelets or leukocytes during experimental extracorporeal circulation could be shown.