We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that itsin vitrostimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of∼3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.