Attention-deficit hyperactivity disorder (ADHD) is thought to have a biologic basis, but the precise cause is unknown. It is one of the neurodevelopmental abnormalities frequently observed in children with generalized resistance to thyroid hormone (GRTH), suggesting that thyroid abnormalities may be related to ADHD. We report a prospective screening study for thyroid abnormalities in 277 children with ADHD by measurement of serum levels of total thyroxine, free thyroxine index, and thyrotropin. Fourteen children with ADHD had thyroid function test abnormalities: six had a normal free thyroxine index and elevated thyroxine level (group 1); three had a high free thyroxine index and a normal thyrotropin level (group 2); and five had a low free thyroxine index with a normal thyrotropin level (group 3). GRTH could not be demonstrated in a detailed study of four of the subjects in whom it was suspected (groups 1 and 2). Although the prevalence of ADHD in subjects with GRTH has been reported to be 46%, the overall prevalence of GRTH must be less than 1:2500 because we failed to detect GRTH in the 277 children with ADHD studied. We conclude that the prevalence of thyroid abnormalities is higher (5.4%) in children with ADHD than in the normal population (< 1%).