Total and cytosolic zinc (Zn) and copper (Cu), cytosolic metallothionein (MT) and the Cu-load of MT were investigated in fetal (22, 24 and 32 gestational weeks) and neonatal (2-15 months) human liver. Whereas the fraction of cytosolic Zn remained constant at 66% of the total independent of the stage of development, the fraction of cytosolic Cu increased from 26% in preterm liver to about 100% within 12 months postnatally. The MT content was higher in fetal than in neonatal liver. There was a linear correlation (r = 0.996) between cytosolic MT and Zn in both fetal and neonatal liver but not between MT and Cu. In contrast to fetal liver, the Cu-load of MT in neonatal liver seems to be determined by the Zn/Cu ratio in the cytosol. The results suggest that MT is involved in the regulation of Cu and Zn metabolism during fetal and neonatal development.