In the TARGET trial, the lower incidence of cardiac events at one month with abciximab compared with tirofiban was attributed to a lack of efficacy in the first hour because of suboptimal dosage. The object of this study was to confirm that high dose tirofibal is associated with over 90% platelet inhibition during the first hour and to analyse the effect of this new dosage on platelet activation. Thirty-three patients treated with clopidogrel and aspirin for an acute coronary syndrome without ST elevation were given before angioplasty a bolus of 25 microg/Kg of tirofiban injected in 3 minutes, followed by an infusion of 0.15 microg/kg/min. Blood samples were taken before the treatment (TO) and at the 45th minute (T1) to measure platelet aggregation induced by ADP, the expression of P-selection, the quantification of circulating monocyte-platelet aggregates and the phospholyration of VASP protein. The results showed that all patients had over 90% (100%) inhibition of platelet aggregation at T1. The expression of P-selection was significantly reduced (T0: 0.195 +/- 0.057 MFI; T1: 0.186 +/- 0.055 MFI, p = 0.03). There was no significant difference in the number of monocyte-platelet aggregates or in the phosphorylation of VASP. In conclusion, a bolus of 25 microg/Kg/3 min of tirofiban provides over 90% inhibition of platelet aggregation in the first hour. The initial platelet proactivator effect at this dosage was shown to have disappeared with an inhibition of platelet activation.