We investigated the thyroid function of 151 children with Down syndrome. Compared with a control group of 89 siblings nearest in age to their brother or sister with Down syndrome the mean TSH value was significantly higher in children with Down syndrome than in the non-Down syndrome children (8.49 μU/ml vs. 3.55 μU/ml). However, the mean T4, levels in both groups were nearly the same (8.36 μg/dl and 8.60 μg/dl). In the Down syndrome group there was a trend for TSH values to increase and for T4 values to decrease with advancing age. Of the 151 patients with Down syndrome, 10 had both significantly elevated TSH levels ( > 9.5 μU/ml) and significantly decreased T4 levels (< 5.5 μg/dl) 21 had abnormally high TSH values (>9.5 μU/ml), 7 had markedly increased T4 levels (> 12.0 μg/dl), and 3 had significantly decreased T4 levels (< 5.5 μg/dl). The intellectual functioning of children with both abnormal TSH and T4 levels was significantly lower (mean IQ 41.7) than that of Down syndrome children with only increased TSH values (mean IQ 53.8) and that of Down syndrome children with normal thyroid function (mean IQ 55.3).This study provides evidence that there is an increased prevalence of thyroid dysfunction in children with Down syndrome. Therefore, children with Down syndrome should have thyroid function studies performed at regular intervals and prompt treatment should be instituted if thyroid dysfunction has been identified.