Background. Recent advances in minimally invasive surgical technology have the potential to lead to new applications outside body cavities. The purpose of the present study was to develop techniques for obtaining endoscopic exposure and access to the pretracheal space in the neck with the goal of performing neck exploration and parathyroidectomy and to evaluate the safety and efficacy of such an approach experimentally. Methods. The technique for endoscopic neck exploration was developed in eight adult mongrel dogs and was further evaluated in a survival dog model and in human cadavers. The pretracheal space was accessed by a 2.5 cm midline incision in the lower neck. This space was expanded with a balloon dissector, and exposure was maintained with an external lift device. A 5 or 10/12 mm midline port and two to four lateral 5 mm cervical ports were placed, and dissection was carried out with pediatric endoscopic instruments and an ultrasonic coagulator. Excised parathyroid tissue was verified histologically. Results. Two-gland parathyroidectomy was successfully completed in five of six dogs; inadequate exposure led to a failed procedure in one animal. Mean operative time was 130 ± 6 minutes, and there were no operative complications. Serum calcium levels did not change significantly after operation (p = not significant). At autopsy, approximately 20 ml of clear sterile fluid was present in the pretracheal space of every dog. In five human cadavers mean dissection time for attempted four-gland parathyroidectomy was 69 ± 38 minutes (range, 45 to 135 minutes). Four of four parathyroids were identified and removed in two patients, three of three parathyroids in one patient, three off our parathyroids in one patient, and two of four parathyroids in one patient. Conclusions. Parathyroidectomy may be performed safely and reliably in an animal model with minimally invasive techniques that can be applied to parathyroid dissection in human cadavers. These results suggest that an endoscopic approach to neck exploration and parathyroidectomy is potentially feasible and may warrant further study in clinical trials.