Radioactive iodine (RAI)-induced changes in the levels of antibodies to the thyroid-stimulating hormone (TSH) re¬ ceptor (TRAb) in patients undergoing treatment for autoimmune thyroid disease have been well documented. Previous studies have reported effects on the overall level of the antibodies present, TSH-binding inhibitory im¬ munoglobulins (TBII), without detailed studies of specific effects on the levels of thyroid-stimulating (TSAb) or thy¬ roid-blocking antibodies (TBAb). More detailed studies have been reported only in individual cases. In this study, the values of TSAb, TBAb, and TBII were measured longitudinally in 33 patients (27 females and 6 males) who re¬ ceived RAI. The bioassays for TSAb and TBAb were performed in JP09 cells. Following RAI, there were signifi¬ cant and immediate effects on the values of TBII in 70% of patients. TBII levels fell in 7 patients (20%) (Group 1), rose in 16 patients (48%) (Group 2) or remained unchanged but elevated in 10 patients (32%) (Group 3). In the Group 1 patients, only TSAb were detectable and none of these patients became hypothyroid after treatment. In the 16 patients in Group 2, increases in TBII were attributable to specific increases in TSAb in 7 (44%), in TBAb in 3 (19%), and in both TSAb and TBAb in 3 (19%). There were 3 patients (19%) in this group in whom there was no detectable TSAb or TBAb activity despite the increase in TBII. Six patients from this group became hypothy¬ roid within 6 months of RAI treatment. In the 10 patients in Group 3, 5 patients (50%) were positive for TBAb only, 2 (20%) were TSAb-only positive, and 3 (30%) were both TSAb-and TBAb-positive. Five patients (50%) in this group became hypothyroid and all had TBAb present in their circulation. Our results show that there are di¬ verse changes in TBII, TSAb, and TBAb following RAI. Hypothyroidism occurred in 33% of the patients treated with RAI therapy and TBAb were present in 75% of these hypothyroid patients. When TBAb were present in the absence of TSAb, hypothyroidism occurred in 6 of 8 versus 3 of 14 where TSAb were present alone (p < 0.05). The development of hypothyroidism within 6 months of RAI treatment was not related to continuation or dosage of an¬ tithyroid drugs and was transient in 50% of patients. We conclude that early hypothyroidism following RAI ther¬ apy is associated with increased TBAb in some patients and that recognition of this clinical situation should avoid unnecessary life-long thyroxine replacement.