The goal of this study was to compare the effects of oxygen deprivation on cellular energy state and pH in the developing and adult rat brain. Relative quantities of phosphocreatine (PC), inorganic phosphorus (P(i)), and nucleoside triphosphates (NTP), and intracellular pH, were determined using in vivo 31P NMR spectroscopy at different postnatal ages (postnatal day (P) 2-6, P9-13, P16-20, P23-27) in the hypoxic rat brain (7 min, 4% O2). While a significant increase in P(i) was seen at all ages during hypoxia, a severe but reversible reduction in concentrations of PC (80-100% decrease) and NTP (40-50% decrease) was observed only at P9-13. This dramatic response was not seen in older (> P16) or younger (< P6) animals. These latter groups responded with moderate decreases in brain PC (50-60% decrease) and NTP (20-40% decrease). In addition, the youngest animals showed much less intracellular brain acidosis than the other age groups. The transient period of development during which the brain exhibits heightened susceptibility to hypoxic energy failure coincides with known changes in brain energy production pathways and susceptibility to hypoxia-induced excitability.