Folic acid deficiency has been reported to produce a substantial change in the ratio of hemoglobin S to hemoglobin A in the blood of individuals having sickle cell trait. Synthesis of the specific β-chains of these hemoglobins was studied before and after folate antagonism was produced by methotrexate administration. Incorporation of L-leucine-14C into β⁰ and βSby bone marrow cells was unchanged as a result of the treatment with methotrexate, indicating that synthesis of these globin chains was not selectively affected by the drug.