To report an epidemic of atypical thyroiditis that occurred in southwestern Europe during 1995.We present the clinical, laboratory, morphologic, and histologic features of 672 cases of thyroiditis and describe the results of treatment.During 1995, atypical thyroiditis was diagnosed in 672 of 725 patients with thyroid disorders encountered at our medical center in Huelva, Spain. Of these patients, 98% were women with normal ovarian function. The clinical findings were acute or subacute manifestation of diffuse nodular enlargement of the thyroid and spontaneous, severe pain on deglutition and palpation of the gland. Initial hematology and serum biochemistry studies, free triiodothyronine, free thyroxine, thyrotropin, and thyroid-stimulating immunoglobulins were in the normal range, but after the second week, the thyrotropin level began to increase. Thyroid antibodies (thyroglobulin and thyroid peroxidase) increased up to 300 times the high-normal level. Ultrasonography exhibited diffuse nodular enlargement of the thyroid gland, with irregular hypoechoic, normal, and hyperechoic zones. Fine-needle aspiration biopsy showed abundant lymphocytic infiltration. The best treatment results were obtained with the combination of levothyroxine and deflazacort. Because the epidemic appeared after a severe drought of 5-year duration (1991 to 1995) and affected women with normal ovarian function, our etiopathogenetic hypothesis was that an estrogen-like chemical substance polluted the area swamps. The high concentration of the pollutant was attributable to diminished water levels (8% of their capacity at the end of the drought period), and this situation may have affected the population through tap water used for human consumption.We describe an atypical autoimmune thyroiditis that affected primarily women of reproductive age, after a severe drought. The main features were a very painful, diffuse nodular enlargement of the thyroid gland, substantially increased thyroid antibodies, good response to levothyroxine and deflazacort combination treatment, and a benign evolution to chronic thyroiditis. Pollutants from various sources should be considered when atypical thyroiditis occurs in any community.