The effects of altered thyroid state on the antioxidant defense system in the liver of differently aged rats were examined. Male rats aged 15, 45 and 75 days were treated with L-thyroxine, T4 (40 g/100 g body mass, s.c., one dose per day) for 14 days (finally aged 30, 60 and 90 days, respectively). The following antioxidant defense enzymes were measured: superoxide dismutases (both copper zinc, CuZn-SOD and manganese containing, Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), glutathione reductase (GR), as well as the content of low molecular mass antioxidant glutathione (GSH). The effect of T4 on antioxidant defense system in the liver differs with respect to age. T4 treatment decreased CAT and GST activities, as well as the content of GSH in animals aged 60 and 90 days. The same treatment elevated GR activity in rats at 30 days of age, this phenomenon was not observed in older animals. The different response of immature rats to thyroxine compared to older animals could be attributed to the differences in thyroxine metabolism and the developmental pattern. Direct effect of T4 on mature rats can be considered as a part of its overall catabolic action.