Determinations of erythrocyte glucose-6-phosphate dehydrogenase, pyruvate kinase and glucose-phosphate isomerase activities have been carried out in jaundiced and non-jaundiced newborn infants at birth and after 5 days of life. Only hyperbilirubinemias of unknown etiology have been considered. Previous investigations have demonstrated that erythrocyte age dependent enzyme activities decrease in the healthy newborn during the first week of life. Following the results of the present paper, jaundiced newborns do not show such a decrease, since a statistically significant difference between paired data of glucose-6-phosphate dehydrogenase and pyruvate kinase in jaundiced and non-jaundiced newborns have been found. It is likely that the lack of decrease of enzyme activities in the jaundiced infants depend upon the loss of oldest red cells with low glucose-6-phosphate dehydrogenase and pyruvate kinase. Our observation suggests the occurrence of a slight hemolysis in newborn infants with hyperbilirubinemia of unknown etiology.