• Intracellular calcium overload has been implicated to be a major factor in triggering cell death after ischemic neuronal injury. We investigated the effects of flunarizine hydrochloride, a calciumoverload blocker, on pressure-induced retinal ischemia in a rat model. Retinal ischemia was induced in albino Lewis rats by increasing the intraocular pressure to 110 mm Hg for 45 minutes. Two regimens of treatment with flunarizine were examined: (1) prophylactic treatment, in which flunarizine was administered before ischemia and in the early phase of reperfusion; and (2) postischemic treatment, in which flunarizine was administered only in the early phase of reperfusion. Injury was evaluated morphologically and morphometrically by measuring the thickness of the inner retinal layers on plasticembedded retinal sections and by counting the retinal ganglion cells on retinal flat preparations. By morphologic and morphometric criteria, a significant but partial protection of the inner retinal layers was noted in the groups given either regimen. This protective effect of flunarizine suggests that elevated intracellular calcium concentration may play an important role in ischemic retinal injury.