Lectin stimulation of human T lymphocytes causes a 7-fold increase in the specific activities of GTP-cyclohydrolase and a 4-fold increase in the specific activities of sepiapterin reductase. GTP-cyclohydrolase activities are maximal after 48 h and subsequently decline, whereas sepiapterin reductase activities contunue to increase during the 72 h period measured. The specific activities of 6-pyruvoyltetrahydropterin synthase remain unchanged upon stimulation. Tetrahydrobiopterin synthesis during blast transformation is thus directed by both GTP-cyclohydrolase and sepiapterin reductase.