In genetically predisposed individuals, autoimmune lymphocytic thyroiditis (LT) is potentiated by excess dietary iodine (I). There have been data which suggest that oxidative stress may have a role in iodine-induced LT. These in vivo studies were undertaken to examine the effect of iodine on intrathyroidal levels of the potent antioxidant glutathione (GSH) and see if the thyroids of LT-prone BB/Wor rats have aberrant GSH responses after iodine-loading. LT-prone BB/Wor, non LT-prone BB/Wor and Wistar rats were randomized to receive either 0.05% I (as Nal) or tap water. Thyroid and liver homogenates were assayed individually for GSH. Following the administration of 0.05% iodine water overnight, all of the animals demonstrated a rise in intrathyroidal GSH regardless of LT-proneness. To determine whether this was a dose-dependent response, Wis rats were randomized to receive tap, 0.0125%, 0.025%, 0.05%, or 0.075% I, overnight. Intrathyroidal GSH levels rose with increasing iodine concentrations peaking at 0.025% I. Hepatic GSH levels were unaltered by iodine treatment. Ten days of 0.05% I water did not result in any difference between the GSH levels of thyroids from treated and control rats. Frozen sections of the thyroids and livers from iodine-treated rats were compared to tap-water controls after staining with Mercury Orange for GSH and Schiff's reagent for evidence of lipid peroxidation. Iodine-treated thyroids had an apparent shift of GSH staining from the apical border to the cytoplasm. However, there was no Schiff's staining indicative of lipid peroxidation in the iodine-treated thyroids.(ABSTRACT TRUNCATED AT 250 WORDS)