The livers of newborn rabbits, mice, Syrian and Chinese hamsters contain high cytoplasmic concentrations of metallothioneins. In the rabbit and mouse the hepatic concentrations of these metalloproteins are highest at, or immediately after birth and then decrease rapidly whereas, in the Syrian and Chinese hamster, maximum concentrations are not reached until 4 and 9 days post partum, respectively. In the human liver the metallothionein concentration appears to be maximal during gestation and is appreciably less in the newborn than the 33-week foetus. In addition to age-related variations in metal content, the metal composition of the hepatic metallothionein fraction also varies with species; that of the rabbit always contains Zn as principal bound metal, that of the mouse or the Chinese hamster usually contains Zn and Cu in ratios greater than unity, whilst that of the Syrian hamster, at least until 14 days post partum, contains more Cu than Zn. In all of these species, as in the human foetus and infant, however the Zn: Cu ratio in the metallothionein varies with age. Values for this ratio, as well as the concentrations of thionein-bound Zn and Cu, in the rodent species seem to be determined by the concentrations of these metals in the whole liver. It is suggested, therefore, that in foetal and newborn animals, thionein synthesis acts as a protective mechanism against excessive amounts of the essential, but potentially toxic Zn and Cu ions, possibly before the development of other control processes.