Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type). In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type). In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [50.0 +/- 12.2% (+/- SD) vs. 4.3 +/- 3.2%; P less than 0.01], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6. Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again. Two patients had a history of habitual ingestion of seaweed (25.4 and 43.1 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily. The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland. These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.