PURPOSE. To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS. This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS. Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS. Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.