BACKGROUND Laparoscopic adrenalectomy has recently been shown to be a safe and effective means of treating adrenal pathology with much lower morbidity than the traditional approach. The majority of reports in the literature involve removal of adrenal tumors. Although open bilateral adrenalectomy has been utilized for persistent Cushing's syndrome following attempted hypophysectomy, there is little data available describing the application of laparoscopic adrenal surgery to this problem. METHODS Four patients with persistent Cushing's syndrome after attempted treatment with hypophysectomy underwent laparoscopic bilateral adrenalectomy at our institution. One procedure was done transabdominally in the supine position. Three procedures were done transabdominally using sequential lateral decubitus positions. RESULTS All procedures were completed laparoscopically. The mean operative time was 4.6 h (range 3.9-5.25). Repositioning and reprepping the patients resulted in a slight increase in operative time, but visualization was improved using the lateral decubitus position. Average blood loss: 156 cc (range 50-300). One patient required early reoperation for bleeding from the left adrenal bed, which was controlled laparoscopically. Three patients were eating the following day and were discharged on postoperative days 1, 2, and 5. The fourth patient remained hospitalized for 18 days due to problems unrelated to surgery. After a mean follow-up of 10 months, all patients have done well and have no clinical or biochemical evidence of recurrent disease. CONCLUSIONS Our clinical experience indicates that laparoscopic bilateral adrenalectomy is a viable treatment option for Cushing's syndrome following failed hypophysectomy.