Median nerve compression is a well-known cause of carpal tunnel syndrome (CTS). Yet, reasons why the most common idiopathic form of CTS develops in certain individuals are not well understood. To further understand the compressive mechanisms at work in CTS development, the authors used ultrasonographic imaging of the median nerve to evaluate 2 patients with CTS. Findings were compared to those of 2 control subjects who did not have CTS. In the patients who had CTS, the transverse carpal ligament was pulled taut by thenar muscle contraction as the flexor tendons tightened, compressing the median nerve between the ligament and tendons. No such compression was observed with the control subjects. Thus, a pathologic mechanism of median nerve compression was confirmed in the patients with CTS. Demonstration of such pathologic mechanisms during prehensile hand movement may improve understanding of how to treat patients with CTS and prevent nerve injury.