Aim: The biological effectiveness of irradiation is influenced not only by the total dose but also the rate at which this dose is administered. Tolerance dose estimates from external radiation therapy with a conventional fractionation protocol require adaptation for application in targeted radionuclide therapy. Methods: The linear-quadratic model allows for calculation of the biologically effective dose (BED) and takes into consideration tissue specific factors (recovery capacity) aswell as dose rate effects (recovery kinetics). It can be applied in radionuclide therapy as well. For relevant therapeutic radionuclides (e. g. ¹⁸⁸Re, ⁹⁰Y, ¹⁷⁷Lu, and ¹³¹I), the effect of different physical decay times and variable biological half-lives on BED was calculated for several organs. Results: BED is markedly increased using ¹⁸⁸Re compared to longer-lived radionuclides. The effect is dose-dependentand tissue-specific, resulting, for example, in higher effects on the kidneys compared to bone marrow. Therefore, in unfavourable conditions (e. g. reduced recovery capacity due to concomitant diseases or previous therapy), the BED may exceed organ dose tolerance. Conclusion: Time-dose-relationships have to be taken into consideration by the calculation of BED for internal radionuclide therapy. The biological effectiveness depends on dose- and tissue-specific factors and is much more pronounced in ¹⁸⁸Re than in ⁹⁰Y and other longer living radionuclides. Determination of organ tolerance dose values should take into account these radiobiological differences, since it is currently not considered in dosimetry programs.