Antithrombotic activity and heparin with endothelium are observed in rats when heparin is administered by the oral route. Peak endothelial concentrations at 6 min suggest rapid absorption. To identify the site of absorption, stomach and duodenum were isolated by tying the pyloric sphincter of male Wistar rats and heparin (unfractionated bovine lung, 60 mg/kg) was administered by stomach tube or injected into the duodenum. Heparin in plasma and aortic endothelium, collected within 15 min, was determined by densitometry following agarose gel electrophoresis with toluidine blue staining. Heparin was recovered in 5 of 10 endothelial (0.136+/-0.068 microg/cm(2)) and 6 of 10 plasma (0.06+/-0.02 microg/ml) samples when administered in the stomach and in 0 of 9 endothelial and 2 of 9 plasma (0.02+/-0.02 microg/ml) samples when injected into the duodenum. To further study heparin distribution, stomach layers were separated and analysed 15 min and 4h following heparin administration by stomach tube. Heparin was recovered in muscle and mucosal layers as well as washes indicating that heparin passes through stomach tissue. Heparin was also recovered from the portal vein, endothelium and lung. These results indicate that heparin is absorbed following oral administration and that the stomach is an important site of absorption.