Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.