in the central nervous system, magnesium ion (mg2+) acts as an endogenous modulator of n-methyl-d-aspartate (nmda)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. in the present study, we investigated the effects of magnesium chloride (mgcl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (dz), on ischemia-induced hippocampal cell death. male wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. mgcl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). dz was always given twice, at 1 and 2 h post-ischemia. thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, n = 34), dz (10 mg/kg, n = 24), mgcl2 (2.5 mmol/kg, n = 10), mgcl2 (5.0 mmol/kg, n = 17), mgcl2 (7.5 mmol/kg, n = 9) or mgcl2 (5 mmol/kg) + dz (10 mg/kg, n = 14). seven days after ischemia the brains were analyzed histologically. fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3%) and ca1 (88.4%) sectors of the hippocampus (p<0.0001, vehicle vs sham). compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86.7-93.4%) and ca1 (lesion: 85.5-91.2%) pyramidal cells (p>0.05). both dz alone and dz + mgcl2 reduced rectal temperature significantly (p<0.05). no animal death was observed after drug treatment. these data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.