It is well recognized that starvation and malnutrition are associated with a low-T3 syndrome in man. A similar condition has been observed after intake of a low carbohydrate hypocaloric diet. However, little is known about the influence of iodine on these conditions. Therefore, we evaluated the effect of iodine supplementation on thyroid function before and after a short-term intake of a low carbohydrate diet in normal subjects residing in an iodine-deficient area. The study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5 females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4 days. Eight subjects received 500 µg iodine (oral) daily beginning 4 weeks before diet. The control group (n = 8) received no iodine. After iodine supplementation, iodine excretion increased from 52 to 405 µg iodine/g of creatinine. Total T4 showed a slight but significant increase (104.2 nmol/lvs. 115.8 µg/dl;p < 0.001);fT4 was unchanged. The intake of the hypocaloric low carbohydrate diet resulted in a striking decrease in both total and free T3 and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were not affected in either group. During diet, iodine administration resulted in a decrease of basal TSH from 2.3 to 1.2 mU/1 (p < 0.05), ΔTSH from 10.3 to 4.5 mU/1 (p < 0.01) and ΔT3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p < 0.01). In contrast, no significant changes of basal TSH and T3 response after TRH were seen during diet in the control group. In conclusion, changes of T3, rT3 and rT3 during caloric restriction occurred irrespective of iodine supplementation. However, significant alterations in basal TSH and T3 response after TRH could only be demonstrated in subjects receiving iodine supplementation.