In a family, a moderate bleeding disorder in two patients has been specified as Glanzmann's thrombasthenia because of characteristic defects in platelet function. Analysis of platelet membrane glycoproteins revealed about a 50% decrease in the amount of GP IIb-IIIa complex (α11bβ3integrin), which appeared normal with respect to electrophoretic mobility, apparent M, and isoelectric behaviour of GP IIb and GP IIIa. Content of platelet fibrinogen (Fg) was normal. [125I]Fg binding to ADP-stimulated platelets was strongly reduced but Kdvalues indicated a much higher affinity of the residual receptors for both [125I]Fg and RGD peptide. Fg bound to the isolated complex as detected by crossed immunoelectrophoresis and there was substantial expression of endogenous Fg on the surface of washed thrombin-stimulated platelets. RGD-peptide induced increased binding of conformation-specific monoclonal antibodies (Mabs) LIBS 1 and PMI-1. Flow cytometric analysis revealed defective binding of nine Mabs, among them two out of three tested antibodies specific for GP IIIa (C 17, AP 5). Results indicate a genetic variant of GP IIb-IIIa complex with the structural abnormality possibly related to defective conformational change upon activation.