Renal tubular reabsorption of NaCl increases during the transition from fetus to newborn. Therefore, we studied the activity of NKA in basolateral membranes (BLM) from proximal tubules of fetal (>60 days gestation; 68 days is term), 3-5 day old newborn and adult guinea pigs. There was a 4-5 fold greater Vmax in newborns than in fetuses (fetuses, 0.40±0.05; newborns 1.95±0.17, adults 3.41±0.53 μmol Pi/mg protein/min., P<0.005) without a significant difference in theKM's for K+ and ATP (which were 2.5 and 0.5 mM, respectively). Western blots of BLM were probed with either an anti-rat NKAα1-subunit antibody or polyclonal antibodies to purified guinea pig outer medullary NKA αβ-heterodimer. Blots were standardized using an anti-rat actin antibody. These blots showed 3-10 fold increases in NKA α- and β- subunit abundances during the transition from fetus to newborn (P<0.005). Finally, Northern blots of guinea pig renal cortical RNA were probed with an antisense [32P]UTP-RNA probe generated from a 332 bp rat cDNA segment of the amino terminus and 5′ flanking region of the α1-subunit of NKA. Blots were standardized using an antisense[32P]UTP-RNA probe generated from a cDNA of the human 18s rRNA. These blots showed no significant differences in α1-subunit mRNA levels when the three age groups were compared. We conclude that there is a marked upregulation of NKA activity and abundance in the newborn proximal tubule BLM, a finding not previously reported. This increase is due to a post-transcriptional upregulation of the NKA α1-subunit and may account for the newborn kidney's enhanced ability to reabsorb NaCl.