The prevalence, characteristics, and evolution of autonomously functioning thyroid nodules (AFTN) were studied in two population groups from northeastern Sicily. One group was living in an iodine-deficient area and another was living in an iodine-sufficient area. The prevalence of AFTN was significantly higher in the iodine-deficient area (4.4% of total patients vs. 2.7%). No significant difference between the two areas was observed in sex and age distribution and size of the nodules. In addition, a higher percentage of patients with toxic nodules (1.3%) was found in the group from the iodine-deficient area. Furthermore, in a selected group of patients followed for 1-6 yr, a higher percentage of patients from the iodine-deficient area had either an increase in the size of the lesion or an increase in thyroid hormone production leading to toxicity. These data suggest that iodine deficiency is one possible factor in the development of AFTN and that iodine deficiency may also be involved in the increased frequency of toxic evolution of these lesions.