Effects of phosphate depletion (PD) in young rats on inorganic phosphate (Pi) and adenine nucleotide metabolism in kidney were examined to evaluate the role of altered adenine nucleotide metabolism in the pathogenesis of renal dysfunctions in PD. Despite a rapid fall in plasma pi, renal Pi and ATP levels did not fall until 2nd and 4th week, respectively. Concomitant with a fall in ATP, the equilibrium constant (Keq) of adenylate kinase decreased, suggesting an altered intracellular Mg ion concentration. The oral Mg supplement prevented a fall in plasma Mg occurring in PD as well as a fall in Keq of adenylate kinase without any effect on a decrease in tissue Pi and ATP. These data indicate that tissue levels of Pi and ATP did not fall until severe PF develops, and a concomitant Mg deficiency may play some role in the pathogenesis of some of the cellular dysfunctions seen in PD. Renal gluconeogenesis was inhibited in renal cortical tubules as early as on the 3rd day of PD. Although the mechanisms for such inhibition of gluconeogenesis are not known, this abnormal cell metabolism may underlie some of the tubular dysfunctions in PD.