The contrasting effects of aspirin on bleeding time (BT) might be related to the drug's inhibitory activity on platelets and vascular prostaglandin I2 (PGI2). To test this, we developed an exchange transfusion model in the rat and studied the BT in animals whose platelets but not vessels had been exposed to aspirin. Rats with severe experimental thrombocytopenia were exchange-transfused with blood from normocythemic rats pretreated with aspirin 6 hr before. The platelet count was raised from 2% to about 70% of basal level and the BT returned to control values even though the platelets neither responded to arachidonic acid nor produced detectable amounts of malondialdehyde and vascular PGI2 was not inhibited. These results indicate that "aspirinated" platelets may be hemostatically active and that the BT is not necessarily affected by unbalanced prostaglandin production in platelets and the vessell wall.