The claim that large, nonspecific doses of vitamins and minerals improve the performance of mentally retarded children has recently reappeared in both the scientific literature and the public media. This hypothesis was examined in a double-blind, case-control study involving 20 home-reared children with Down's syndrome between 5 and 13 years of age. Children were randomly assigned by matched pairs to either a vitamin/mineral group or placebo group for an 8-month study period. No significant group differences or suggestive trends were found in any tested area of development or behavior, including intelligence (IQ), school achievement, speech and language, and neuromotor function. No group differences in appearance, growth, or health were seen. No support was found for the orthomolecular hypothesis in school-aged children with Down's syndrome.