1. The effect of moderate endurance exercise on blood glucose concentration and on glucoregulatory hormones was studied in nine thyrotoxic and five myxoedematous humans before and 3 months after anti-thyroid and substitution therapy, respectively. 2. At rest, the fasting concentrations of insulin and pro-insulin correlated positively with the prevailing total tri-iodothyronine concentration, whereas the concentrations of noradrenaline and cortisol correlated inversely with the tri-iodothyronine concentration. 3. During exercise the plasma insulin, pro-insulin and C-peptide concentrations decreased. The plasma glucagon concentration increased slightly in thyrotoxic patients before and after treatment and was largely unchanged in myxoedematous patients in either state. 4. The plasma noradrenaline concentration increased before and after treatment in both groups, with concentrations two times higher in the myxoedematous than in the thyrotoxic patients. Treatment for 3 months did not change this pattern. The plasma adrenaline concentration increased in both groups, but in the untreated thyrotoxic patients the increase was two to three times greater than that after treatment or that in the myxoedematous group. 5. The blood glucose concentration decreased in eight of nine untreated thyrotoxic patients, but was largely unchanged after treatment or in the myxoedematous patients. A strong negative correlation was found between the decline in blood glucose concentration and the increase in plasma adrenaline concentration in the thyrotoxic group. 6. Thus, during exercise untreated thyrotoxic patients are prone to hypoglycaemia, show an inadequate glucagon response, and exhibit a large counter-regulatory increase in plasma adrenaline concentration.