Incorporation of radioactivity from L,-3-14C-serine into DNA was at least 2-fold higher in fetal human liver slices (413 ± 34 dpm/mg wet weight/h) than in mature human liver slices (213 ± 21 dpm/mg wet weight/h); the incorporation into RNA by fetal human liver slices (49 ± 6 dpm/mg wet weight/h) was 10-fold lower than into DNA. These incorporations were not limited by endogenous methionine. When the serine concentration of the liver slices is taken into consideration, the synthesis of DNA utilizing the (3-carbon atom of serine was 4-fold higher in fetal human liver slices than in mature human liver slices. Those results suggest that the modified pathways of transsulfuration of methionine metabolism and remethylation of homocysteine to methionine may be an adaptation by the human fetus for diverting the β-carbon atom of serine into de novo synthesis of DNA.