Diffusion-weighted (DW) and T2-weighted (TW) magnetic resonance (MR) imaging techniques have successfully detected ischemic changes in a variety of stroke models. Recently, it has been reported that there are age-dependent differences in the MR imaging changes observed during and after an episode of cerebral hypoxia/ischemia. The biophysical mechanisms for MR changes remain undefined. We hypothesized that the age-dependent MR changes in hypoxia/ischemia (occlusion of the right carotid artery plus exposure to 8% oxygen) were due to the developmental differences in hypoxia/ischemia-induced changes in brain water, cell volume control and/or cell death. Thus, we investigated the correlation between MR changes and alterations in brain water, Na -K+-ATPase activity, cytochrome oxidase activity and cell death at various times following the start of hypoxia/ischemia until 24 hours of reperfusion in neonatal (1 week old) and young (4 week old) rats. The results suggest that hypoxia/ischemia-induced T2 and DW changes reflect alterations in water content and Na+-K+-ATPase in neonatal brain, respectively. However, there is only a partial correspondence in young brain suggesting that there might be other factors contributing to the developmental differences in the visibility of hypoxic/ischemic MR changes. (Abstract shortened by UMI.)