The effects of methionine on deoxyribonucleic acid (DNA) synthesis of B₁₂-deficient megaloblastic bone marrow cells were investigated over a wide concentration range. Deoxyuridine (UdR) incorporation and the UdR suppression test were employed as an indicator for DNA synthesis. Only a low and limited concentration range of methionine improved significantly the impaired DNA synthesis of megaloblastic cells, although the extent of improvement was less than those by either B₁₂ or folate. Higher concentrations of methionine ( ?? 150 μg/ml), however, were suppressive for both megaloblastic and normoblastic cells. In contrast, homocysteine did not affect DNA synthesis of megaloblastic cells at low concentration. Improving effect of methionine at low concentration appeared to be characteristic to megaloblastic cells, since such effect disappeared on hematologic recovery following B₁₂ administration.