Sinus nodes of five symptomatic patients with the long QT syndrome were surgically excised and followed by permanent electronic pacing as part of a new surgical treatment. We examined those sinus nodes by light and electron microscopy with tissue that was promptly fixed at the time of surgery. All five sinus nodes were similarly abnormal. By light microscopy we found distinctive focal fibrosis, some degenerating myocytes and neural elements, and numerous narrowed small vessels. Except in the nerves there was no evidence of inflammation. In electron micrographs the mitochondria within nodal myocytes were abnormally abundant, remarkably pleomorphic, and smaller than those in normal human sinus nodal cells. The ultrastructural features of the degenerated nodal cells were typical of apoptosis, characterized by the absence of inflammation, well-preserved mitochondria, the presence of apoptotic bodies, phagocytosis of these cells by neighboring myocytes, and especially in smooth muscle cells of arterioles, nuclear chromatin margination and nucleolar disintegration. Apoptotic degeneration of nodal myocytes was stochastic, with adjacent cells appearing unaffected. Focal ischemia caused by narrowed vessels may be a contributory factor, and the nerves may harbor some viral infection, but for the nodal myocytes the abnormality appears to be primarily apoptosis, sometimes called programmed cell death. Both the typically episodic clinical features and the terminal event in fatal cases of the long QT syndrome may be due to apoptosis.