Cholesterol deficiency is believed to result in fragile plasma membranes. It remains unclear whether a reduction in the amounts of both mevalonate pyrophosphate decarboxylase (MPD), which is involved in cholesterol biosynthesis, and cholesterol content occurs in the cerebrum and brain stem (diencephalon and midbrain) in or near the sites of strokes in stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we investigated whether a reduction in both the amounts of MPD and cholesterol content corresponded to the sites of strokes in the SHRSP brain. The results obtained suggested that a reduction in the amount of MPD was involved in the decrease observed in cholesterol content, and was also important as a risk factor for stroke in SHRSP because the reductions in cholesterol content and MPD protein levels were associated with the sites of strokes. The mechanism responsible for reducing MPD protein levels in the brains of SHRSP differed with each region.