Inclusion Criteria:

• Patients must have a serious measurable neurological deficit on the NIH Stroke Scale due to focal brain ischemia.
• An NIH Stroke Scale score >5 at the time the rt-PA is begun.
• Age: 18 through 85 years (i.e. candidates must have had their 18th birthday, but not had their 86th birthday).
• Intravenous rt-PA therapy must be initiated within 3 hours of onset of stroke symptoms.

Exclusion Criteria:

• History of stroke in the past 3 months.
• Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
• Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal.
• Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mmHg or aggressive measures to lower blood pressure to below these limits are needed.
• Presumed septic embolus.
• Presumed pericarditis including pericarditis after acute myocardial infarction.
• Recent (within 30 days) surgery or biopsy of parenchymal organ.
• Recent (within 30 days) trauma, with internal injuries or ulcerative wounds.
• Recent (within 90 days) severe head trauma or head trauma with loss of consciousness.
• Any active or recent (within 30 days) serious systemic hemorrhage.
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with INR > 1.7.
• Baseline lab values: positive urine pregnancy test, glucose < 50 or > 400 mg/dl, platelets <100,000 /mm3, Hct <25 %, or creatinine > 4 mg/dl.
• Ongoing renal dialysis, regardless of creatinine.
• If heparin has been administered within 48 hours, the patient must have a normal partial thromboplastin time (PTT).
• Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days.
• Seizure at onset of stroke.
• Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
• Other serious, advanced, or terminal illness or any other condition that the investigator feels would pose a significant hazard to the patient if rt-PA or eptifibatide therapy were initiated.
• Patients whose peripheral venous access is so poor that they are unable to have two standard peripheral intravenous lines started.
• Current participation in another research drug treatment protocol. Patient cannot start another experimental agent until after 90 days.
• Informed consent is not or cannot be obtained.
• Any known history of amyloid angiopathy.
• High density lesion consistent with hemorrhage of any degree.
• Significant mass effect with midline shift.
• Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment.