OBJECTIVE To investigate the effect of ascorbic acid [vitamin C (VC)] on liver damage parameters in the lead-exposed mice, when given in combination with thiamine [vitamin B1 (VB(1))] at different concentrations. METHODS Sixty-six male mice were randomly assigned into 11 groups (n = 6). Mice in Group I were supplied with only the tap water as the drinking water; mice in Group II were provided with a tap water containing 0.2% lead acetate; mice in Group III-XI were given different dose of VC (140, 420, 1260 mg kg(-1) bw) and VB(1) (10, 30, 90 mg kg(-1) bw) according to 3 x 3 factorial design by oral gavages, along with ingestion of 0.2% lead acetate. After 42 test days, DNA damage of liver cells was assessed using single-cell gel electrophoresis. The apoptosis rate of liver cells was determined by flow cytometry. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood and the level of reduced glutathione (GSH) in liver cells were measured based on individual biochemical reactions. RESULTS Compared with the Group I, sub-chronic lead ingestion (Group II) resulted in a significant decrease of Hb, GSH-P(X), SOD in blood and GSH level in liver cells; lead exposure induced also a significant increase in DNA damage and apoptosis of liver cells (P < 0.05). Supplementation with VC and VB(1), however, reversed these effects. The best effective combination was VC (420 mg kg(-1) bw) and VB(1) (10 mg kg(-1) bw), followed by the combination of VC (420 mg kg(-1) bw) and VB(1) (30 mg kg(-1) bw). But no reversion was shown in the combination of the highest combination of VC (1260 mg kg(-1)) and VB(1) (90 mg kg(-1)). CONCLUSIONS These findings strongly indicated that combination of VC and VB(1) can lessen the damage to liver cells from oxidative stress induce by lead, but the antioxidant effects are dependent on their concentrations.