Trichothiodystrophy, or sulfur-deficient brittle hair, is a clinical marker for a neuroectodermal symptom complex that usually features mental and physical retardation and may also include nail dystrophy, lamellar ichthyosis, ocular dysplasia, dental caries, and decreased fertility. Cystine-deficient hair is common to all patients. The hairs from two new patients were studied, and the most distinctive microscopic hair findings were striking bright and dark bands seen with polarizing microscopy using crossed polarizers. To date, all hair samples showing this banding have had an abnormally low sulfur content. Two-dimensional electrophoresis on the two protein fractions of the abnormal hair confirmed that the abnormality is caused by decreased synthesis of high-sulfur matrix proteins. Disturbances of the transport or utilization of sulfur-containing amino acids in other neuroectodermal tissues may be proposed to account for the various disease features in these persons.