Most assays of thyroid stimulating immunoglobulin (TSI) are unsuitable for the quantitation of TSI during the treatment of Graves' hyperthyroidism because assay insensitivity results in some negative responses. Therefore the sensitive cytochemical bioassay was used to investigate the effect of carbimazole on TSI levels as a possible mechanism for the induction of the increased remission rate which is characteristic of thionamide therapy. Twelve patients were studied before therapy for de-novo Graves' hyperthyroidism; seven patients consented to a detailed prospectively study during block-replace therapy with carbimazole 10mg 6 hourly with a later addition of T3 20 micrograms 6 hourly when biochemically euthyroid. In addition thyroid hormone or T3 suppressed technetium (99m Tc) thyroidal uptake was monitored at between weekly and 3 monthly intervals, as well as the clinical findings, total T4 total T3, TSH, antimicrosomal antibody titers and immunoglobulins IgG, IgM and IgA. TSI was detected in all patients before treatment but there was no correlation with any other pretreatment measurements. During therapy TSI fell (in three different patterns) in 6 out of 7 patients studied for between 14-55 weeks (mean 29 weeks). TSI remained unchanged in one patient. Only the 99m Tc uptake correlated with TSI activity in the treated patients as a group (r = 0.71, p less than 0.001). TSI remained detectable in all patients, even in 4 patients in whom T3 suppression of 99m Tc was demonstrated. There is some evidence for a carbimazole effect lowering TSI activity, however relapse rate did not support this. T3 suppressed 99m Tc uptake may be a sensitive in vivo marker of TSI activity.