The thyroid function of 44 subjects with Down syndrome who were between 2 and 51 years of age was assessed. Three patients (7%) had hypothyroidism, and in 2 of them high titers of antimicrosomal antibody were detected. Seven additional subjects (16%) had low-borderline thyroid function, 6 with elevated thyroid stimulating hormone. These 7 subjects constituted the cohort for an evaluation of the short-term benefits of thyroid hormone supplementation in the low-borderline thyroid functional state. A double-blind crossover drug placebo trial failed to document any cognitive, social, response time, or physical changes attributable to the 8- to 14-week drug treatment period compared to an untreated matched control group. Results provided no evidence for the efficacy of short-term thyroid hormone therapy for this population.