OBJECTIVE Spontaneous improvement occurs in about one-half of patients with primary hypothyroidism who reside in an iodine-sufficient area of Japan, but the pathogenetic factors related to reversible hypothyroidism are still not fully understood, We therefore investigated the clinical features and prognosis of patients with reversible hypothyroidism with or without iodine excess and antithyroid antibodies. DESIGN Amelioration of hypothyroidism was diagnosed when the elevated serum TSH concentrations (serum TSH concentration greater than or equal to 40 mU/l) decreased by 50% or more during an iodine restriction period of 2-15 weeks without replacement therapy. Reversible hypothyroidism occurred in a post-partum group (n = 20) and a nonpost-partum group (n = 91). The latter was then further classified into chemical (n = 28), immunological (n = 20), and mixed (n = 43) groups, according to the presence of iodine excess (serum non-hormonal iodine level > 50 mu g/l or a history of excess iodine ingestion), antithyroid autoantibody, or both, respectively. MEASUREMENTS clinical characteristics and long-term prognosis were compared among the four groups. The rate at which hypothyroidism recovered was expressed as the number of days required for a 50% decrease in the serum TSH concentration, The level of thyroid echogenicity was measured by 10-MHz ultrasonography, RESULTS In the chemical group, the mean age, male:female ratio, and serum non-hormonal iodine concentrations were all higher than those in the immunological group. The estimated rate at which hypothyroidism recovered was rapid (6.1 +/- 3.1 (mean +/- SD) days), the levels of thyroid echogenicity were near normal, and a histological examination (n = 7) revealed either colloid goitre or a normal thyroid in the chemical group, In the immunological and post-partum groups, the recovery rate was slow (16.8 +/- 9.6 days and 16.2 +/- 5.8 days, respectively). The levels of thyroid echogenicity were markedly reduced but increased after the spontaneous recovery of the thyroid function in both groups. Aspiration cytology suggested lymphocytic infiltration in ail patients examined in the immunological (n = 6) and post-partum groups (n = 4), Relapse to overt hypothyroidism was observed more frequently in the immunological (38%) and mixed groups (35%) than in the chemical group (5%). CONCLUSION Thyroid damage was more severe, recovery slower and the rate of relapse higher in the immunological than in the chemical type of reversible hypothyroidism.