The venous-arterio prostaglandin [PG] E concentration gradient across the thyroid was measured in 5 patients undergoing subtotal thyroidectomy for Graves'' disease. This gradient (161 .+-. 14 pg/ml; mean .+-. SE) was significantly greater than that found in 11 patients undergoing surgery for hyperparathyroidism and thyroid nodules (64 .+-. 20 pg/ml; P < 0.01). There is apparently a net increase in PGE output by the thyroid gland in Graves'' disease, but the thyroid cell-type responsible for this increased PGE output is unknown. In contrast to previous reports, thyrotropin (TSH) did not stimulate thyroid cell PGE generation in vitro, providing evidence against a role for TSH in this phenomenon. Administration of maximal doses of indomethacin to 2 thyrotoxic patients did not significantly alter peripheral thyroid hormone concentrations. Thyroidal PGE has a function other than to stimulate thyroid hormone secretion in Graves'' disease.