This study confirms observations made in a former study of plasma of preterm and term newborn infants with intrauterine malnutrition during the first month of life and extends to the lactational period. The free fraction of l-tryptophan, the precursor amino acid of brain serotonin synthesis, is significantly elevated up to 3 months of age. According to previous results, which demonstrated that l-tryptophan and serotonin synthesis are increased in the brain of gestationally malnourished rats, the present data in humans malnourished early in life strongly suggest that the elevation of the free fraction of l-tryptophan in plasma provides an increased amount of the precursor molecule to pass across the blood-brain barrier and activates the synthesis of brain serotonin. Because serotonin has been found to have a possible neurotrophic role in the fetal brain, any alteration of its metabolism in this period could reflect as a permanent change in brain neurogenesis. The data suggest that the free fraction of plasma l-tryptophan may be an indirect marker of changes in brain serotonin synthesis in these patients. Additional data on the functional relevance of the brain serotonergic system in humans are required to support this hypothesis.