In Graves' hyperthyroidism, suppression of serum TSH after restoration of normal serum T4 and T3 with treatment has been attributed to binding of TSH-receptor antibodies to TSH receptors in the pituitary. Accordingly, the relationship between TSH and serum thyroid stimulating immunoglobulin (TSI) was examined during follow-up of patients with Graves' hyperthyroidism.23 patients with Graves' hyperthyroidism were identified who met the inclusion criteria of at least 24 months follow-up after initiation of methimazole and availability of concurrent measurements of serum TSH and TSI.TSI disappeared in 12 patients (Group A) and persisted in 11 patients (Group B). Initial T4 was not significantly different between the 2 groups. However, TSI was significantly lower in Group A than Group B [median (interquartile range) 179 (152-212)% vs 255 (208-369)%, p=0.0009]. In Group A, TSH normalized during treatment, and this anteceded disappearance of TSI by a significant time interval [median (interquartile range) 6 (3-8) months vs 15 (11-20) months, p=0.005]. In Group B, TSI persisted in all patients during follow-up ranging from 24 to 73 months. No correlation was found to exist between serum TSH and TSI, and for Group B TSI at final follow-up was not significantly different from the initial value [median (interquartile range) 255 (208-369)% vs 236 (160-310)%, p=0.4].These findings do not support the suggestion that TSI has a direct suppressive effect on TSH secretion.