High-frequency ultrasound biomicroscopy is a new method of examining subsurface anterior segment structures of the eye at microscopic resolution. The sclera has a high internal reflectivity and can be differentiated from the cornea, and overlying and underlying tissue. Using this modality, we examined 18 patients with various manifestations of scleral disease. Localized anterior staphyloma could be differentiated from other causes of a black spot on the scleral surface. Episcleral thickening could be differentiated from involvement of the sclera itself. Different patterns of scleral involvement could be imaged including diffuse low-reflective mottling, low-reflective nodules extending into the scleral substance, and scleral thinning. Scleral thinning could be assessed and quantified. Underlying changes in the vitreous could be detected. Ultrasound biomicroscopy was a useful adjunct to clinical examination in the assessment of anterior scleral disease.