This study describes the anatomical basis of direct visualization of the radial nerve and of fracture reduction in humeral shaft nailing and reports first clinical results. Fourteen cadavers were random selected and dissected in order to determine the exact course of the radial nerve in relationship to anatomical landmarks. In individuals with a total humeral length between 25-33 cm the radial nerve was found to cross the humeral shaft exactly in the middle of the long axis of the humeral shaft. The average distance from the lateral epicondyle to the point were the radial nerve penetrates the lateral intermuscular septum was 11.9 +/- 1.0 cm, the distance from the posterior tip of the acromion to the crossing of the nerve with the medial border of the humeral shaft was 12.9 +/- 1.5 cm. Using these landmarks in six clinical cases fracture reduction, visualization of the radial nerve and intramedullary nailing could be achieved with endoscopic control. There were no surgical complications such as secondary radial nerve palsy, hematomas or wound healing problems. With the use of the endoscope the number of secondary radial nerve palsies associated with intramedullary humeral shaft nailing might be reduced in the future.