Hypoxic/ischemic (H/I) brain injury is thought to be mediated via the N-methyl-D-aspartate receptor complex, which can be blocked by the magnesium ion. Striatal medium spiny neurons abundantly express N-methyl-D-aspartate receptors and are known to be injured after H/I. Thus, the aim of this study was to investigate the effect of postinjury magnesium treatment on the total number of medium spiny neurons in the striatum after perinatal H/I injury in the rat. Anesthetized postnatal day (PN) 7 rats underwent common carotid artery ligation followed 2 h later by exposure to hypoxia for 1.5 h. Contralateral hemispheres served as controls as did animals exposed to normoxia. Immediately after hypoxia or normoxia, the magnesium groups received s.c. injections of 300 mg/kg MgSO4. Control, hypoxic or normoxic animals received NaCl injections. This continued daily until PN13. Eleven matched-for-weight H/I pups were injected in total. A power calculation showed that 11 pups per treatment group would permit detection of a treatment difference of 32% or more. Animals were killed on PN18, and 40-µm serial sections were cut through each entire striatum. The total number of the predominant medium spiny neurons within each striatum was stereologically determined via the use of an unbiased optical dissector/Cavalieri combination. It was found that postinjury magnesium treatment did not improve neuronal survival by 32% or more in the striatum. The results suggest that magnesium treatment after perinatal H/I damage in the rat is not markedly neuroprotective for striatal medium spiny neurons.