In clinical ischemia/reperfusion injury, damage resulting from oxidative and nitrosative stress is generally considered crucial for graft functioning. Yet, there is reasonable doubt that modern clinical transplantation including orthotopic liver transplantation (OLT) is associated with elevation of oxidative and nitrosative stress upon organ reoxygenation. We measured two biomarkers of oxidative stress, 15(S)-8-iso-prostaglandin F 2α (15(S)-8-iso-PGF 2α ) and cis-epoxyoctadecanoic acid (cis-EpOA), in human plasma during the entire time duration of OLT in nine patients suffering from end-stage liver disease. No considerable concentration changes of 15(S)-8-iso-PGF 2α and cis-EpOA were observed in plasma, indicating lack of oxidative stress. Creatinine-corrected urinary excretion of 15(S)-8-iso-PGF 2α in two urine samples collected 40-60 min and 60-240 min after reperfusion did not increase significantly. Previously, we found in the same patients that nitrosative stress, measured as 3-nitrotyrosine and 3-nitrotyrosinoalbumin, is elevated in the patients but did not change during OLT. 15(S)-8-iso-PGF 2α , cis-EpOA, 3-nitrotyrosine and other widely used biomarkers of oxidative stress, notably malondialdehyde (MDA), are produced both by chemical and enzymatic reactions. This important issue is rarely considered in the area of oxidative and nitrosative stress. In addition, many widely used analytical approaches such as the total antioxidant capacity (TAC) assay to quantitate oxidative and nitrosative stress in health and disease and during clinical transplantation lack reliability. New basic concepts of oxidative and nitrosative stress need to be drafted and implemented in vitro as well as in vivo in experimental and clinical settings.