Purpose: The purpose of the study was to evaluate changes in biologically effective dose (BED) in the targeted tumor due to varying number of treatment fractions in the case when alpha and beta radiosensitivities of malignant cells are heterogeneous., Methods: The approach used in the current study relies on the linear-quadratic (LQ) model. Within the framework of this model, we consider changes in the biologically effective dose in the treatment target ( B E D tar ) caused by varying number of fractions under the condition of fixed BED in the affected normal tissue ( B E D nt )., Results: In this study, we analytically derive the necessary and sufficient condition which ensures that, compared to standard fractionation, hypofractionation increases B E D tar in the case of heterogeneous radiosensitivities in the treatment target. We also derive expression for dose per fraction which maximizes B E D tar . In addition, variations in B E D tar with number of fractions were determined numerically for several clinical cases by using spinal cord as an example of serial organ at risk (OAR)., Conclusions: The results from this study demonstrate that intratumor heterogeneity influences radiobiological properties of different fractionation regimens as follows: (a) variations in B E D tar caused by varying number of fractions can be nonmonotonical and (b) there exist optimum dose per fraction and number of fractions which maximize B E D tar under the condition of fixed biologically effective dose in the affected OAR., (© 2019 American Association of Physicists in Medicine.)