GABA is the main inhibitory neurotransmitter in the adult brain. However, GABAergic transmission is depolarizing during early postnatal development, suggesting that changes in the expression of cation-Cl- co-transporters regulating neuronal Cl- homeostasis underlie the ontogeny of GABAergic functions. The developmental changes in the expressions of Cl- co-transporter mRNAs in the neocortex were in opposite directions for NKCC1 (Cl- uptake) and KCC2 (Cl- extrusion). In the newborn, NKCC1 mRNA expression was highest in ventricular zone followed by cortical plate, and then by Layer V/VI, while the reverse was true for KCC2 mRNA. The [Cl-]i levels were in the same rank order as for NKCC1 mRNA. Thus, the ontogeny of Cl- homeostasis in neocortical neurons could be regulated via the differential expression of NKCC1 and KCC2.