Patients with cerebral ischemia or brain tumor have been reported to exhibit an increase of deoxygenated hemoglobin (deoxy-Hb) together with an increase of oxygenated hemoglobin (oxy-Hb). However, the physiological mechanisms underlying this hemodynamic response pattern are unclear. In this study, we performed a simulation using the balloon model (Buxton et al., Magn Reson Med 39:855-864, 1998). We hypothesized that the oxygen extraction rate during the rest period (E-0) in the patients is larger than in normal subjects, because the cerebral blood flow and the speed at which the blood passes through the brain tissues are lower in the patients. The simulation result showed an increase of deoxy-Hb as well as oxy-Hb, especially when E-0 is extremely high. Thus, the results of our simulation suggest that the increase of deoxy-Hb during activation in patients with ischemia or brain tumor is caused by an increased oxygen extraction rate at rest, compared with that of healthy adults.