Oxy-Pherol-ET (OP-ET) is an artificial blood substitute composed of perfluoro~ributylamine (FC-43) emulsified with pluronic (FC-68) and hydroxyethyl starch as a plasma expander. This blood substitute is quite unique in that it has a high oxygen and carbon dioxide carrying capacity and is inert. In order for OP-ET to work, it must co-exist in circulation with blood components. This research project has been an investigation of the effect of OP-ET on the circulation regulatory agents (hormonal, etc). The aorta and vena cava were examined to assess the influence of OPET on the structural components of circulation. Since the kidney plays an important role in the overall regulation of circulation, the influence of the OP-ET on its function and structure were examined also. Stimulation of the renin-angiotensin system by hemorrhage, low sodium diet (LSD), and reduced renal perfusion pressure resulted in an increased release of renin in animals treated with OP-ET. Animals previously exchange-transfused with OP-ET were subsequently monitored daily for changes in weight, water intake, and urinary salt and water output. In OP-ET treated animals weight increase was when slow compared to control animals. The water intake of the animals exchange-transfused animals was substantially greater than control animals for the same time period. Animals prepared with indwelling catheters and exchange-transfused with OP-ET were monitored for their ability to respond to pharmacological concentrations of catecholamines and angiotensin II. Under these conditions animals showed no significant difference in blood pressure response when compared to control animals that were exchange-transfused with donor animals' RBCs and treated similarly with angiotensin and catecholamines. Previously transfused animals were monitored to determine the effect of OP-ET on the kidney. Under these conditions there was a diuretic-induced immediate increase in urinary sodium excretion and a gradual increase in urinary potassium. These were expected responses for this diuretic agent. Scanning electron microscopy (SEM) of exchange-transfused animals did not reveal observable differences within the endothelium of the aorta. The vena caval endothelium of the exchange-transfused animals showed no significant changes. There were no observable alterations in the glomerular capillaries by 7 days post-transfusion. The data warrant the conclusion that mechanisms which normally regulate the circulation still function in the presence of the blood substitutes used in this study. The use of OP-ET has great potential in emergency medicine and remote areas of the world where whole blood would be difficult to maintain.