The syndrome of primary lateral sclerosis (PLS) has been reported clinically on many occasions. Pathologic confirmation in the modern era, however, has generally been lacking. In a recently reported case of PLS, the disorder was complicated by a pontine infarct. We describe a 65-year-old woman whose illness began with spastic dysarthria, which gradually worsened to the point that 18 months later she could barely utter a sound. Meanwhile, dysphagia, brisk reflexes, and a pseudobulbar affect had developed. Three years after onset she had a spastic contractured right-sided hemiplegia and walked with short shuffling steps. The spasticity slowly progressed, and she died of aspiration pneumonia 3.5 years after the onset of dysarthria. Neuropathologic examination showed bilateral atrophy of the precentral gyri, which microscopically showed a paucity of Betz cells. There was loss of myelin throughout the corticospinal system, yet the anterior-horn cells of the spinal cord and hypoglossal nuclei were well preserved. Intracytoplasmic eosinophilic inclusion bodies, of unknown cause and significance, were observed in occasional motor neurons, one in the hypoglossal nucleus and two in spinal cord anterior horns. Clinically and pathologically, this case meets the criteria for PLS.