To determine if introduction of iodized salt induces thyroid autoimmunity in goitrous children, we conducted a prospective trial in iodine-deficient Moroccan schoolchildren (n = 323). Local salt was iodized at 25 microg iodine per gram of salt and distributed to households. Before introduction of iodized salt and at 10, 20, 40, and 52 weeks, we measured antithyroid peroxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), urinary iodine (UI), and thyroid hormones, and examined the thyroid using ultrasound. At baseline, median UI was 17 microg/L and the prevalence of goiter and hypothyroidism was 72% and 18%, respectively. Provision of iodized salt maintained median UI at 150-200 microg/L for the year (p < 0.0001). There was a significant increase in mean total thyroxine (T(4)) and a significant reduction in the prevalence of hypothyroidism (p < 0.001). There was a transient increase in the prevalence of detectable antibodies after introduction of iodized salt (p < 0.0001) with levels returning to baseline at 1 year. Only congruent with 1% of children had elevated TPO-Ab and none had elevated Tg-Ab over the course of the study, and no child with elevated TPO-Ab had abnormal thyrotropin (TSH) or T(4) concentrations. None developed clinical or ultrasonographic evidence of thyroid autoimmune disease and/or iodine-induced hypothyroidism or hyperthyroidism. Rapid introduction of iodized salt does not provoke significant thyroid autoimmunity in severely iodine-deficient children followed for 1 year.