Numerous investigations document that exposure to low dose external therapeutic radiation leads to the development of benign and malignant thyroid neoplasms. There is considerable controversy, however, concerning whether radioactive iodine (I-131) causes thyroid cancer. The aim of this investigation was to examine our experience and that in the literature related to this problem. From 1982 to March 1993 seven of 373 patients (1.9%) with thyroid cancer who were treated by one surgeon had a history of treatment with radioactive iodine for Graves' disease and toxic nodular goiter. Sixty-five patients have previously been reported in the literature from 1957 to present. Our patients (five women, two men) ranged in age from 26 to 80 years (mean 57 years). The interval between the exposure to the internal radiation and development of cancer ranged from 3 to 29 years (mean 11.4 years), and the mean age at the time of I-131 treatment was 45 years (18-76 years). The therapeutic dose of I-131 was 5 to 100 mCi (mean 25.3 mCi) in our patients. Two of our patients received I twice. The age of patients reported in the literature at the time of I-131 treatment ranged from 7 to 74 years (mean 48 years). The mean therapeutic dose of I-131 was 20.6 mCi (1.25-180.0 mCi) and the latent period was documented for a mean 8.7 years (0.25-28.0 years) in these patients. Three of 29 patients in the literature received I-131 twice. Fine-needle aspiration cytology of thyroid nodules was positive for cancer in six of our patients (86%). All patients were treated by total thyroidectomy, and three of them had a modified neck dissection. Six of our seven patients had invasive papillary thyroid carcinoma (stage III disease), and the seventh patient had extensive nodal metastasis and intrathyroidal invasion. Invasion into adjacent muscle and soft tissue were found in four patients, and two had tracheal invasion. Two patients had lymph node metastases. There were no postoperative complications. One patient (14%), however developed recurrent papillary and anaplastic thyroid cancer in his left neck and mediastinum 2 years after total thyroidectomy. He had extensive pulmonary metastases and malignant pleural effusions and died 23 days after a left modified radical neck dissection. In conclusion, radioactive iodine in doses to treat Graves' disease may increase the risk of developing thyroid cancer. These cancers are discovered at a later stage and appear to be aggressive.