Since thyroid peroxidase (TPO) is essential in thyroid hormone biosynthesis, we evaluated whether a correlation exists between TPO activity and iodothyronine stores in human thyroid tissues from nodular goiters with scintigraphically "cold" (N = 10) or "hot" (N = 7) nodules, diffuse toxic goiters (N = 6), and in normal rat thyroids (N = 18). T4, T3 and rT3 were significantly correlated (rs greater than 0.84, P less than 0.001) in human thyroid tissues, although no correlation between TPO activity and any of the iodothyronines was found. Both TPO and the iodothyronines in human goitrous thyroid glands showed great variation which may mask an underlying relationship. However, this is unlikely since no correlation was found between the much less variable TPO and T4 or T3 in the normal murine thyroid. Other factors related to iodothyronine synthesis and secretion must be at least as important as TPO in determining thyroidal stores.