Abstract. A longitudinal study of red cell enzyme activity in newborn infants of low birth weight has been conducted over the first 2 months of life. The enzymes investigated are aeetylcholinesterase (EC 3.1.3.7), an integral part of the red cell membrane and subnormal in AB0 hemolytic disease of the newborn; and glucose-6-phosphate dehydrogenase (EC 1.1.1.49), an intracellularly-located, sex-linked enzyme, implicated in neonatal jaundice and of significance in drug-induced hemolytic anemias. Acetyleholinesterase activity, which is lower in normal full-term newborn infants and in low birth weight infants than in adults, was further diminished during the initial weeks of life of the infants of low birth weight and the higher levels of activity, characteristic of adult red cells, had not appeared by 2 months of age. By contrast, red cell glucose-6-phosphate dehydrogenase activity, which is higher in full-term newborn infants and in infants of low birth weight than in adults, did not diminish as a function of age and the lower adult levels were not discernible by 2 months of life.