Greene melanoma in the anterior chamber of rabbits was irradiated by protons to find the isoeffect curve for proton irradiation fractionated into one, two, three or four doses. The isoeffect curve for tumor tissue remained constant between one- and three-dose fractionations and rose with four-dose fractionation. The isoeffect curve for normal tissue approximately followed the Ellis equation. Therefore, the optimal irradiation schedule should be in the range of three fractions because this best spares normal tissue while delivering a tumoricidal dose to the lesion. The relative reduction of the total dose from four- to one-dose fractions of intraoperative irradiation should be 20%.