The effect of low-molecular-weight dextran and aspirin on platelet deposition after transluminal coronary angioplasty was studied in a normal canine model. Eighteen anesthetized, open-chest dogs were separated into 4 groups. All dogs received 3,000 units of intravenous heparin 10 to 20 minutes before the procedure. Dogs in Group 1 served as controls and were given no further treatment. Dogs in Group 2 received low-molecular-weight dextran by continuous intravenous infusion at a rate of 20 ml/hour for 1 hour before balloon inflation. Dogs in Group 3 were given 500 ml of low-molecular-weight dextran as an intravenous bolus over 1 hour, beginning 4 hours before the procedure. Dogs in Group 4 were fed 20 mg/kg of aspirin 3 hours before angioplasty. The dogs were killed 10 minutes after angioplasty and the arterial segments subjected to balloon inflation submitted for electron microscopic analysis. An additional group of 10 dogs was used to assess the bleeding times and platelet counts from control and drug-treated dogs. Drug treatment was associated with significant prolongation of the bleeding time and reduction in platelet number. Extensive endothelial desquamation in the area of balloon angioplasty was observed in all dogs. However, no appreciable qualitative difference in either the degree or extent of rapid platelet deposition to the exposed subendothelium was discernible between the control and any of the treatment groups. These results do not confirm previous observations with low-molecular-weight dextran. Further work on the initial and long-term platelet response after endothelial injury should be undertaken in a primate atherosclerotic model.