Dietary restriction in experimental rodents, either by calorie restriction (CR) or by every-other-day fasting (EODF), was shown to protect against cancer and increase lifespan. One of the suggested hypotheses to explain the beneficial effects of dietary restriction is that the diet stabilizes the integrity of the genetic information. The effects of EODF on the spontaneous frequency of sister chromatid exchanges (SCE) and chromosomal aberrations (CA) were examined in bone-marrow cells of 3-mo-old Wistar male rats. After 12 wk of EODF diet, significant reduction in the frequency of SCE and total number of CA was observed. Data indicate a protective effect of EODF diet against spontaneous mutations in rats.