Patients with spontaneous non-aneurysmal subarachnoid hemorrhage (non-aSAH) are considered to have a benign illness in contrast to patients with aSAH. The occurrence of the systemic inflammatory response syndrome has been linked to worse outcomes in patients with aSAH. We analyzed systemic interleukin (IL)-6, a proinflammatory cytokine, to determine whether its concentration differs between patients with non-aSAH and those with aSAH, reflecting the more benign illness. Daily systemic IL-6 levels were measured in the acute phase in 11 patients with non-aneurysmal perimesencephalic SAH (pmSAH), with bleeding strictly located around the midbrain, and in nine patients with non-aneurysmal non-perimesencephalic (non-pmSAH), with hemorrhage extending into adjacent cisterns (group 1). IL-6 levels were compared with those from patients suffering from aSAH with cerebral vasospasm (CVS) (group 2) and without CVS (group 3). The mean IL-6 level (±standard error of the mean) was significantly lower in group 1 compared to group 2 (9.9±1.9 vs. 29.1±6.7pg/mL, p=0.018). The difference in mean IL-6 level between group 1 and 3 fell short of significance (9.9±1.9 vs. 14.9±1.1pg/mL, p=0.073). Patients in group 1 had a significantly better outcome (Glasgow Outcome Scale score 4-5) compared to group 2 (p<0.001) and a trend towards better outcome compared to group 3 (p=0.102). A subgroup analysis revealed a higher mean IL-6 concentration in patients with non-pmSAH compared to patients with pm-SAH (p=0.001). We concluded that systemic IL-6 concentration reflects the severity of the inflammatory stress response and course of the illness. The more benign illness and good prognosis of patients with pmSAH or non-pmSAH in contrast to patients with aSAH is reflected by the lower concentrations of IL-6.