PURPOSE. Studies suggest that reduced ocular perfusion pressure in the optic nerve head (ONH) increases the risk of glaucoma. This study tested a hypothesis that the magnitude of blood flow change in the ONH induced between two same intraocular pressure (IOP) alterations depends on the level of mean systemic blood pressure (BP). METHODS. In eight anesthetized rhesus monkeys, systemic BP was maintained at either a high, medium, or low level (n 6 each, ranging from 51-113 mm Hg); IOP was rapidly altered from 10 to 30 mm Hg and then to 10 mm Hg manometrically. Blood flow in the ONH (BFONH) was repeatedly measured with a laser speckle flow graph for 10 minutes at each IOP level period. The BFONH and relative changes to the baselines at each measured time point were calculated and compared lon- gitudinally among the three BP groups. RESULTS. There was no statistically significant difference in mean baseline BFONH across the BP groups. In the high-BP group, BFONH had no significant change during the IOP alter- ations. However, the same IOP alterations caused a significant BFONH change in the two lower BP groups. The duration of the BFONH changes from baseline to a peak and to a steady state was significantly delayed in the two lower, but not the higher, BP groups. CONCLUSIONS. Systemic BP plays an important role in maintaining the normal autoregulation of the ONH, and it became deficient in the lower BP groups. In patients with glaucoma, a normal, sustained BP may be important to prevent worsening glaucoma. © Association for Research in Vision and Ophthalmology.