Eight patients with Williams syndrome and 6 with Down syndrome, matched for age and full-scale IQ, underwent detailed neurologic testing as part of a large multidisciplinary research center study. Williams syndrome patients were small for gestational age and often had histories of failure-to-thrive and feeding problems as infants. Half of the Williams syndrome patients had epilepsy. On neurologic testing, Williams syndrome patients had greater difficulty with gross and fine motor coordination, oromotor skills, and cerebellar function than did those with Down syndrome. The neurologic distinctions between these 2 groups may reflect an underlying, as yet undefined, metabolic defect in Williams syndrome.