We have examined insulin action on glucose metabolism in six hypothyroid patients before and after regular thyroid hormone treatment, and in six healthy volunteers before and after transient induction of moderate hyperthyroidism. Insulin was infused under euglycaemic and eukalaemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced decreases in amino acid levels. Glucose kinetics were assessed using a primed continuous infusion of [6,6-(2)H(2)]glucose. The results showed that basal plasma insulin and glucose levels (i.e. before infusion) were similar in each case. Despite similar insulin infusion rates, the plateau value of insulin was lower after thyroid treatment in both hypothyroid patients and healthy volunteers. The rate of exogenous glucose needed to maintain plasma glucose at a steady-state level was increased by thyroid hormone in hypothyroid patients (P <0.05), but not in healthy volunteers. Thyroid treatment resulted in a significant increase in basal glucose disposal in both groups (P <0.05). Insulin, in conjunction with glucose and amino acids, significantly stimulated glucose disposal (P <0.05) under all conditions. The incremental increase in glucose disposal after infusion tended to be higher following thyroid hormone treatment, but this was not statistically significant. However, the ratio of the incremental increase in glucose disposal to the increase in plasma insulin was significantly improved after thyroid hormone treatment in hypothyroid patients (P <0.05). It was also increased in healthy volunteers, but not significantly. We conclude that thyroid hormones improve the ability of insulin to stimulate glucose disposal related to insulinaemia. This phenomenon may be highly sensitive, because it was only apparent at low thyroid hormone levels.