Although viral infection has been suspected as the cause of some thyroid disorders, there has been limited data to support this contention seriously. Now we report the first evidence that lymphocytic choriomeningitis virus can persist in the thyroid gland, particularly thyroid epithelial cells in which thyroglobulin (Tg) the precursor of thyroid hormone, is synthesized. Concomitant with the infection of these cells is a significant reduction in Tg mRNA and in the level of circulating thyroid hormones. Another virus (lactate dehydrogenase virus) that causes persistent infection but does not replicate in the thyroid gland failed to alter levels of circulating thyroid hormones. These observations in an experimental model support the hypothesis that viruses may account for some thyroid disorders in man.