Oxidative stress as a mediator of hepatic tissue damage concurrent with Leishmania (L.) chagasi infection was investigated. Chemiluminescence in liver supernatant of hamsters infected with Leishmania (L.) chagasi showed a ratio of 1.53/mg protein and 2.10/liver weight 90 days after infection when compared with the control. The malondialdehyde (MDA) levels also increased significantly both with and without addition of Fe³ /ascorbic acid in the reaction mixture, with a ratio of 2.12 and 1.55/mg protein or 2.91 and 2.12/liver weight, respectively. The parasite burden in the spleen, as a measure of infection severity, was 9.1 ± 1.33 × 10⁸ parasites/organ. On the 10th day of infection, the chemiluminescence also was significantly higher in infected hamsters than in the controls (ratio = 1.36/mg protein or 1.34/liver weight); however, the MDA levels were not different from those of controls. After 90 days of infection, significant correlations were observed between chemiluminescence and MDA concentration with and without the presence of Fe³ /ascorbic acid (r = 0.54, P = 0.0001; r = 0.56, P = 0.0001; respectively). The high infection/control ratio of both chemiluminescence and MDA concentration and the significant correlation between those events strongly indicate the occurrence of oxidative stress and lipid peroxidation as a mechanism of liver damage in cases of chronic infection by L. chagasi. The significant increase in chemiluminescence at 10 days of infection demonstrates that oxidative stress occurs very early, first consuming the antioxidants and then inducing lipid peroxidative damage later in the chronic stage of this disease.