Hepatocytes are highly dependent upon appropriate oxygen provision for activity and viability. However, oxygen delivery to hepatocytes cultured within a hollow fiber bioreactor is believed to be problematic because of large diffusion distances, a high hepatocyte oxygen consumption rate and low aqueous media oxygen solubility. Supplementation of bioreactor media with bovine red blood cells (bRBCs) is one means of improving oxygen delivery to hepatocytes as hemoglobin contained within bRBCs binds oxygen. The impact of supplementing hepatocyte culturing media with bRBCs (approximately 5 x 10(8) bRBCs/ml) on hepatocyte activity (albumin and lactate production and glucose consumption) was studied. Decreased hepatocyte lactate production to glucose consumption ratios were found for the case when bRBCs were added to circulating culturing media, which indicated the presence of a more aerobic environment in comparison to the control (no bRBC supplementation). Additionally, albumin synthesis was found to be improved when the circulating media was supplemented with bRBCs. Our results thus support the use of bRBCs to improve oxygen delivery to hepatocytes maintained within a hollow fiber bioreactor.