The combination of aspirin and dipyridamole is currently used to prevent intimal hyperplasia and to improve long-term vein graft patency following myocardial revascularization. Preliminary studies indicate that cod-liver oil, rich in eicosapentaenoic acid, an unsaturated fatty acid, may also be effective in the prevention of intimal hyperplasia. Twenty-four mongrel dogs were used to compare the effectiveness of aspirin-dipyridamole and cod-liver oil on vein graft intimal hyperplasia following arterial bypass. Forty-eight segments of undistended autologous external jugular vein were interposed between bilaterally divided femoral arteries. All animals received a 2% cholesterol diet for 1 week before and 6 weeks after operation. Eight controls received the diet alone. Eight other animals received dipyridamole (2.5 mg per kilogram of body weight) two days before operation and dipyridamole (2.5 mg/kg) and aspirin (30 mg/kg) daily for 6 weeks after operation. Another 8 animals received cod-liver oil containing 1.8 gm of eicosapentaenoic acid daily 1 week before and for 6 weeks following operation. Serum cholesterol increased similarly in all groups; it rose from 4.5 +/- 0.2 mm/L to 8.3 +/- 0.8 mm/L in the controls, to 7.2 +/- 0.5 mm/L in the aspirin-dipyridamole group, and to 7.1 +/- 0.5 mm/L in the cod-liver oil group (p less than 0.01). Prothrombin time, partial thromoboplastin time, total platelet counts, and bleeding times were unchanged. Intimal hyperplasia was measured at 6 weeks with a Zeiss computerized microscope; 376 +/- 25 measurements were made from each graft. The intima increased from 4.5 +/- 0.2 to 83 +/- 10 micron in the control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)