BACKGROUND The aim of the study is to evaluate the limits of the compensatory mechanisms and the tissue damages caused by the low oxygen content during severe normovolemic hemodilution in pigs. METHODS The experimental procedure was performed in 10 animals after general anaesthesia was induced and iso-hypervolemic hemodilution to Hct 10% was maintained for five hours without any intensive care. Hemodynamic, biochemical and ultrastructural parameters were detected before and at the end of hemodilution in addition to analysis of oxygen delivery/uptake and mitochondrial enzymes function. RESULTS The collected data show: the initial good compensatory mechanism was subsequently exhausted; five animals demonstrated cardiac ischemia and low CO and two of them died before the end of the experiment; no hemodynamic and hemoxymetric data predicted the cardiac ischemia; the dilution caused alterations of some detected biochemical parameters such as hemocoagulation; no evidence of morphologic and ultrastructural tissue damage or interstitial edema; decreasing in mitochondrial enzymes activity significant only for NADH-related. CONCLUSIONS In conclusion, it seems that, in pigs at least, the compensatory mechanisms can keep a sufficient tissue oxygen supply throughout the experimental time with the exception of cardiac muscle.