[en] Purpose/Objective: Linac based stereotactic radiosurgery (SRS) may be performed with a wide range of flexibility, and overall treatment times vary substantially between institutions with respect to the number of arcs, isocenters, and couch rotations employed. At the present time protocols (RTOG 93-05) for SRS do not provide for a treatment delivery time requirement. However, variations in SRS treatment plans may not be biologically iso-effective when a great deal of time is required for intermittent treatment delivery with a large number of arcs, isocenters, and couch angles versus a continuous single isocenter treatment with a gamma knife. The intent of this research is to quantify the decreased toxicity of intermittent radiation exposures and permit the delivery of a biologically iso-effective dose. Materials and Methods: Human tumor cells (U-87MG) were irradiated with various treatment schemes to simulate continuous and intermittent exposures during SRS. Cultured cells were irradiated in vitro with 6 MV x-rays to 12 Gy at a constant dose rate of 2.4 Gy/min. 'Arcs' were simulated by dividing the total radiation dose into equal increments of 8 or 16 min, resulting in irradiation schemes with single, 2, 4, 6, and 8 exposures. The relative percent survival of the different radiation dose delivery schemes was quantitated using standard clonogenic survival analyses, and the significance levels were determined using the Student's t-test. Results: The in vitro experiments demonstrated a significant reduction in biological radiation effect with up to 6- fold increases in cell survival for intermittent vs. continuous irradiation schemes. For a total dose of 12 Gy the percent survival for 16 min intervals was 1.2% for 8 exposures, 0.7% for 6 exposures, 0.6% for 4 exposures, 0.4% for 2 exposures, and 0.2% for a single exposure. Survival curves for doses of 3, 6, 9, and 12 Gy delivered at varying intervals have been used to determine iso-biological effective values for total treatment dose, total treatment time, exposure interval, and dose per exposure for a continuous vs. intermittent SRS treatment plan. Conclusion: The reduced effect of the linac based intermittent irradiation schemes is most likely due to repair processes after radiation exposure, such as PLDR and SLDR, which can occur during the 3 to 15 min intervals between radiation increments of intermittent SRS treatments. The phenomenon of PLDR and SLDR counteracting radiation induced damage in delayed plating and split-dose experiments is well known, but has not been applied to standardize the biological effect of SRS. Having described the decreased toxicity of intermittent radiation exposures, this data can be used to predict correction factors that should permit delivery of biologically iso-effective doses in SRS. These efforts are critical for protracted SRS treatments but can be expected to be even more important when stereotactic radiotherapy is employed with fraction sizes closer to conventional doses