To examine the fractionation effect of stereotactic body radiation therapy with a heterogeneous dose distribution. Derived from the linear quadratic formula with measurements from a hypothetical 2-cm radiosurgical tumor, the threshold percentage was defined as (α/β(tissue)/α/β(tumor)), the balance α/β ratio was defined as (prescription dose/tissue tolerance*α/β(tumor)), and the balance dose was defined as (tissue tolerance/threshold percentage). With increasing fractions and equivalent peripheral dose to the target, the biological equivalent dose of "hot spots" in a target decreases. The relative biological equivalent doses of serial organs decrease only when the relative percentage of its dose to the prescription dose is above the threshold percentage. The volume of parallel organs at risk decreases only when the tumor's α/β ratio is above the balance α/β ratio and the prescription dose is lower than balance dose. The potential benefits of fractionation in stereotactic body radiation therapy depend on the complex interplay between the total dose, α/β ratios, and dose differences between the target and the surrounding normal tissues.