Among 83 consecutive patients operated on for thyrotoxicosis at the Mayo Clinic between January 1, 1980 and May 1, 1986, four had a combination of pathologic findings that were similar and unexpected: involutional changes; degenerative and destructive follicular lesions; and zones of fibrosis. These four, but none of the remaining 79, were being treated with amiodarone for cardiac tachyarrhythmias; this drug is known to be taken up by the thyroid gland. Characteristically, small groups of involuted follicles exhibited varying degrees of damage ranging from degenerative changes in a few lining cells to total follicular destruction. Damaged follicular cells were swollen and featured granular or vacuolated cytoplasm. This type of cytoplasmic alteration has been reported to occur in pneumocytes and hepatocytes damaged by amiodarone. Therefore, the drug probably is the cause of the thyroid cell damage, and follicular disruption (with consequent release of iodothyronines into the circulation) is likely to be an important contributor to the associated thyrotoxicosis.