Potential intrinsic activating properties are probably the most controversially discussed issues with respect to GP IIb/IIIa blockers, especially since clinical trials with oral GP IIb/IIIa blockers revealed disappointing results. Based on the finding that currently clinically used GP IIb/IIIa blockers are ligand mimetics, experimental data are discussed, demonstrating an intrinsic activating effect of ligand mimetic GP IIb/IIIa blockers that potentially results in fibrinogen binding to alpha(IIb)beta(3) and in platelet aggregation. Furthermore, the inhibitory effect of aspirin on GP IIb/IIIa blocker-induced platelet aggregation is discussed as a clinically relevant finding. Finally, the potential association of GP IIb/IIIa blocker-induced thrombocytopenia with platelet activation is described.