Coho salmon (Oncorhynchus kisutch) and chinook salmon (Oncorhynchus tshawytscha) from Lakes Ontario, Michigan, Erie, or Huron were found to suffer epizootics of thyroid hyperplasia and goiters which appeared to have an environmental etiology. There were 13-fold differences in goiter prevalence within the Great Lakes, and the differences in goiter frequency were correlated with the degree of thyroid hyperplasia. A means of assessing the degree of thyroid hyperplasia (thyroid index) is described, and the derived index was used to facilitate statistical interlake and interspecies comparisons. Despite the hyperplastic (or goitered) condition in all prespawning or spawning Great Lakes salmon, serum thyroid hormone levels were generally higher than in prespawning coho salmon from the Fraser River, British Columbia, indicating that the Great Lakes fish were not necessarily hypothyroid. The hyperplastic lesions appear to undergo progressive changes: (a) large follicles, partly colloid depleted, surrounded by cuboidal epithelial cells; (b) small follicles, largely colloid depleted, surrounded by columnar epithelial cells (in this form, the follicles commonly assume a trabeculate arrangement); (c) "microfollicles" with greatly enlarged columnar epithelial cells encompassing very small follicles; (d) apparently afollicular lesions with little or no colloid in evidence. There was some evidence of benign invasiveness, although the lesions generally resembled simple hyperplastic parenchymatous goiters seen in humans.