Ozone (O3) therapy forms part of a group of complementary and alternative medical therapies and is gaining more and more interest worldwide. There is, however, some concern regarding O3-toxicity and uncertainty about the effectiveness of O3-therapy. In this study we investigated the possible protective effects of the plasma antioxidant defense system during O3-AHT. Venous blood from six apparently healthy human donors was collected. In one part of the study a precise volume of blood was mixed >with an equal volume of O2/O3 gas mixture containing 20 or 80 µg/ml O3 for 20 min. In the other part, the plasma was washed out, the cells resuspended in a buffered phosphate solution and treated with same concentrations of O3. Control samples was not treated or treated with O2. Ozone-AHT caused increased plasma hydroperoxide levels and glutathione ratio. Antioxidant enzyme (catalase, glutathione reductase, glutathione peroxidase) activity of peripheral blood mononuclear cells (PBMC) decreased, whereas superoxide dismutase levels increased slightly. Plasma antioxidant capacity decreased. These effects were more evident in the absence of plasma antioxidants. Therefore the damaging effects of O3 were quenched by the antioxidants present in plasma.