Purpose: The aim of this study was to determine the differences in renal damage particularly associated with the effect of a small dose per fraction with a constant total dose. Methods and Materials: Guinea pigs, 12-week-old English Hartley females, were used. The animals were divided into five groups according to irradiation schedule: No irradiation (control group); 2.0 Gy × 1/day, 5 fraction (f)/week (wk), 40 f, total 80 Gy (Group CF-2.0 [CF = conventional fractionation]); 1.0 Gy × 2/day, 10 f/wk, 80 f, total 80 Gy (Group HF-1.0 [HF = hyperfractionation]); 3.0 Gy × 1/day, 5 f/wk, 27 f, total 81 Gy (Group CF-3.0); and 1.5 Gy × 2/day, 10 f/wk, 54 f, total 81 Gy (Group HF-1.5). Only unilateral irradiation was performed. A histologic analysis was performed before irradiation and at 6 and 12 months after the completion of irradiation. The severity and severity ratios of urinary tubule atrophy, the number of large nuclei per unit area in the renal tubules, the average diameter of the glomeruli, and the number of cells composing the glomerulus were used as parameters for evaluating renal damage. Results: In Groups CF-2.0 and CF-3.0 (the conventional fractionation [CF] groups), all the renal tubules showed severe atrophy 12 months after irradiation. On the other hand, only 20% of the renal tubules showed slight atrophy in Group HF-1.0 at 12 months. In Group HF-1.5, 70% of the renal tubules were atrophic at 12 months. The number of large nuclei markedly increased in Groups HF-1.0 and HF-1.5 (the hyperfractionation [HF] groups) at 12 months, whereas the number was very low in the CF groups at 12 months. Only in Group HF-1.0 had the average diameter of glomeruli not shrunk at 12 months. The number of cells composing the glomerulus in the CF groups markedly decreased at 12 months. The number of cells in the HF groups was also reduced, however the reduction was not as severe as that observed in the CF groups. Conclusion: 1.0 Gy per fraction delivered by HF greatly reduces renal damage even in the 80 Gy–irradiated kidney, which is one of the most radiosensitive organs.