This study aimed to determine the osmolality that peripheral venous endothelial cells can tolerate and to clarify the relationship between tolerance osmolality and duration of infusion. Nutrient solutions of 539-917 mOsm/kg, prepared to have no acidic effect, were infused into rabbit ear veins, and the veins were examined histopathologically. In each experiment of 8-, 12-, or 24-h infusion. the higher osmolality solutions caused some phlebitic changes, such as loss of venous endothelial cells, inflammatory cell infiltration, and edema; however, the lowest osmolality solution caused few changes. Infusion of 120 mL/kg of 814 mOsm/kg solution caused phlebitis at 5 or 10 mL.kg(-1).h(-1), however, the same volume of the same solution scarcely caused phlebitis at 15 mL.kg(-1). h(-1) because of the shortened infusion duration. These results suggest that the tolerance osmolality of peripheral venous endothelial cells with poor blood flow is about 820 mOsm/kg for 8 h, 690 mOsm/kg for 12 h, and 550 mOsm/kg for 24 h, and that the tolerance osmolality falls as the duration of infusion increases. In conclusion, hypertonic solutions should he infused at as high a rate as is clinically acceptable and compatible with nutrient bioavailability because increasing the infusion rate reduces the duration of infusion and phlebitis. Nutrition 1998:14:496-501. (C)Elsevier Science Inc. 1998.