We identified 35 patients who had undergone stereotactic radiosurgery (SRS) for their biochemically proven Cushing's disease in order to assess the efficacy of SRS with regard to control of hypercortisolism, improvement of clinical features and prevention of tumor progression, and subsequent incidence of hypopituitarism. Seventeen (49%) patients achieved control of their cortisol levels following SRS; the mean time to normalization was 7.5 months (range: 1-33). Four (19%) patients experienced recurrent hypercortisolism at a mean time of 35.5 months following therapy (range: 17-64). Control of tumor progression was achieved in 91% patients. Fourteen (40%) patients demonstrated a new pituitary deficiency following SRS. Our results suggest that cortisol levels are normalized more efficiently and with a lower recurrence rate with SRS than with conventional fractionated external beam radiotherapy (EBT). We have confirmed the near 100% tumor control rate reported with SRS. The percentage of patients developing pituitary insufficiency following SRS is less than that of patients having undergone EBT; however, deficits occurred up to 10 years posttreatment. We advocate the use of SRS as the primary therapeutic modality in those patients who are poor surgical candidates, or as the adjunct treatment to microsurgery in eliminating residual tumor cells or disease that is not easily amenable to resection.