Background-Oxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke-induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F-2 alpha (iPF(2 alpha)-III). Methods and Results-An OMWW extract (5 mg/kg, providing 414 mug/kg of hydroxytyrosol) was administered to rats daily for 4 days, during which time the animals were exposed to sidestream smoke for 20 minutes once a day. Daily urines were collected, and the urinary excretion of g-iso-PGF(2 alpha) was evaluated as an index of oxidative stress-induced in vivo lipid peroxidation, The exposure of rats to passive smoking increased the urinary excretion of 8-iso-PGF(2 alpha) by 44+/-4.2% at 48 hours and by 55+/-10% at 96 hours. Treatment with the OMWW extract was able to completely prevent the increase at 48 hours and resulted in lower increments (34+/-18% versus 55+/-10%) of 8-iso-PGF(2 alpha) excretion at 96 hours. Conclusions-A low dose of hydroxytyrosol, administered through OMWW, reduces the consequences of sidestream smoke-induced oxidative stress in rats.