In order to further elucidate the pathogenesis of the direct carotid cavernous fistulas (dCCF) clinical, patho-anatomical, and physico-mechanical studies were performed. In 27 of 42 patients the dCCF were found to be localized in the segment C4 (according to Teufel, 12), in 13 patients in segment C2 and in only 2 patients in segment C3. The patients with dCCF in segment C4 were significantly younger than those with dCCF in the segments C2 or C3. In none of the patients fractures of the bony walls of the cavernous part of the internal carotid artery (ICA) could be ascertained. On human cadavers it was affirmed that the cavernous branches of the ICA arise nearly exclusively from the top of segment C3 and from the lateral wall of segment C2. The strength of the wall of the cavernous part of the ICA was shown to decline with age as revealed by means of a tensile machine. There were no significant differences between the four segments investigated. As revealed by roentgenograms the distensibility of the ICA within its coverings was shown to be greatest in the segments C2 and C4 and lowest in segment C3. A sudden increase of the intraluminal pressure ruptured the ICA exclusively in the segments C2 and C4. Histological preparations revealed that the trabeculae of the cavernous sinus insert tangentially into the adventitia of the ICA. Taken together these findings strongly support the view that the dCCF are mainly due to a sudden increase of the intraluminal pressure of the ICA.