N-Methyl-D-aspartate (NMDA) receptors play an important role in the development of neuronal connections in the retina and visual cortex, and in synaptic plasticity in the hippocampus. The objective of this study was to determine whether the sensitivity of hippocampal NMDA receptors to magnesium, glycine or NMDA changes during development. Xenopus oocytes were injected with mRNA prepared from hippocampi from rats of different ages, and NMDA receptor properties studied under voltage clamp. Voltage-dependent block of the NMDA receptor by magnesium was studied with voltage steps of -90 mV to -30 mV, in increments of 10 mV, during application of 100 microM NMDA, 3 microM glycine and 0-1000 microM Mg2+. The IC50 of Mg2+ for blocking NMDA receptor-mediated currents varied e-fold (2.72-fold) for approximately every 15 mV of membrane potential in the middle range of membrane potential (-70 to -50 mV), but the relationship between log[IC50] for Mg2+ and membrane potential was not linear, as would be expected for simple channel block. The slopes of the curves did not change with development, indicating no change in the voltage-dependence of Mg2+ block with age. However, the IC50 of Mg2+ block did change with age at every membrane potential tested. NMDA receptors expressed from mRNA isolated from 14-15 day old rats were nearly 2-fold less sensitive to block by Mg2+ (IC50 = 33 microM at -60 mV) than those from 1-2 day old rats (IC50 = 18 microM).(ABSTRACT TRUNCATED AT 250 WORDS)