Levels of circulating thyroid stimulating hormone (TSH), tetraiodothyronine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5' triiodothyronine (reversal T3 or rT3) were measured in 25 children with trisomy of chromosome 21, also known as Down's syndrome (DS), and in 14 normal children. In subjects with DS TSH levels were increased, while plasmic levels of rT3 were decreased. No alteration in T3 and T4 levels was observed. Before zinc supplementation, plasmic levels of zinc and thymulin, a zinc dependent thymic hormone, were significantly decreased in DS children. After four months of dietary supplementation with zinc sulphate, a normalization of plasmic zinc, thymulin and TSH levels was observed. Plasmic levels of rT3 significantly increased, and after zinc treatment no difference was detectable between DS children and normal children. Clinical evaluation of the health status of DS children showed that zinc supplementation decreased the incidence of infectious diseases and improved school attendance. Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland.