Cerebral vasospasm and delayed cerebral ischemia remain an unsolved problem in patients with aneurysmal subarachnoid hemorrhage (SAH). In theory, high-dose magnesium sulfate (MgSO(4)) therapy offers vascular and neuroprotective benefits and is therefore currently under evaluation. The intensity of the inflammatory response after SAH is associated with the outcome. The aim of the current study was to evaluate a possible link between the inflammatory response and MgSO(4) therapy, since magnesium (Mg(2+)) has anti-inflammatory properties. In 15 patients with SAH, inflammatory cytokine levels in the cerebrospinal fluid (CSF) and peripheral blood were determined daily using an enzyme-linked immunosorbent assay between day 4 and day 12. Eight patients were treated with standard therapy alone (group 1) and seven patients were treated with an additional, high-dose of MgSO(4) (group 2). Serum Mg(2+) levels in group 2 were significantly higher compared to group 1: 1.48 ± 0.04 mmol/L versus 0.90 ± 0.01 mmol/L, ρ<0.001. Interleukin-6 (IL-6) in the CSF was significantly lower in group 2 compared to group 1: 6680 ± 989 vs.11079 ± 1277 pg/mL, ρ = 0.021. A trend towards lower systemic IL-6 levels was found in group 2: 58 ± 7 versus 104 ± 21 pg/mL, ρ = 0.052. Systemic IL-1β levels were significantly lower in group 2: 0.66 ± 0.11 and 0.15 ± 0.01 pg/mL (ρ<0.001), while the CSF levels did not differ. Tumor necrosis factor-α levels did not differ between the two groups. Although there were more patients with favorable outcome in group 2, the difference was not statistically significant. This was probably due to the small sample size. The results indicate a suppression of inflammatory cytokine release, in particular IL-6, in patients treated with high-dose MgSO(4). These results call for further studies of the effect of Mg(2+) on the inflammatory signaling pathway with regard to delayed cerebral ischemia following SAH.