Carnosine has antioxidant properties and is efficient in the treatment of chemically-induced inflammatory lesions in animals. However, some studies question its biological significance as antioxidant and show lack of protection and even pro-oxidant effect of carnosine in systems containing nickel and iron ions. The ability of carnosine to: (1) reduce Fe(3+) into Fe(2+) ions; (2) protect deoxyribose from oxidation by Fe(2+)-, Fe(3+)-, and Cu(2+)-H(2)O(2)-EDTA systems; (3) protect DNA from damage caused by Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems; (4) inhibit HClO- and H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence was tested in vitro. At concentration 10 mM carnosine reduced 16.6+/-0.5 nmoles of Fe(3+) into Fe(2+) ions during 20 min. incubation and added to plasma significantly increased its ferric reducing ability. Inhibition of deoxyribose oxidation by 10 mM carnosine reached 56+/-5, 40+/-11 and 30+/-11% for systems containing Fe(2+), Fe(3+) and Cu(2+) ions, respectively. The damage to DNA was decreased by 84+/-9 and 61+/-14% when Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems were applied. Combination of 10 mM histidine with alanine or histidine alone (but not alanine) enhanced 1.3 and 2.3 times (P<0.05) the DNA damage induced by Fe(2+)-H(2)O(2)-ascorbate. These amino acids added to 10 mM carnosine decreased 3.1-fold (P<0.05) its protective effect on DNA. Carnosine at 10 and 20 mM decreased by more than 90% light emission from both chemiluminescent systems. It is concluded that carnosine has significant antioxidant activity especially in the presence of transition metal ions. However, hydrolysis of carnosine with subsequent histidine release may be responsible for some pro-oxidant effects.