The sensitivity of 6-phosphofructo-2-kinase to glucagon and cyclic AMP was studied during the perinatal period. In liver homogenates from foetal and neonatal rats, incubation with cyclic AMP produced inactivation of 6-phosphofructo-2-kinase 3 h after birth. The maximal effect was obtained 12 h after birth. In primary cultures of hepatocytes from 22-day-old foetuses, glucogon induced an inhibition of 6-phosphofructo-2-kinase that required 45 min to reach the half-maximal effect. Cycloheximide prevented the glucagon-induced changes in this activity from cultured foetal hepatocytes. These results suggest that the adult form of 6-phosphofructo-2-kinase is rapidly induced after birth, probably by the hormonal changes that occur in this period.