Exposure of human blood ex vivo to oxygen-ozone (O2-O3) using either dialysis exchangers or normal oxygenators gives rise to a number of problems, one of which linked to platelet activation, leads to rapid occlusion and no gas exchange. Semipermeable membranes were found unsuitable because, except for one, they were gas-transfer inefficient, allowed ultrafiltration and were more or less vulnerable to O3. Over the last three years we have examined several types of hydrophobic O3-resistant hollow fiber capillaries but, if the polypropylene surface is not properly coated, there is platelet aggregation and blood coagulation. These problems while far less relevant with O2 alone, become prohibitive in the presence of ozone. Recently new oxygenators have been prepared with special materials to make them more biocompatible and it has become possible to oxygenate and ozonate up to 5L of blood in about an hour, thus making the treatment of critical patients feasible.