Percutaneous intranodular ethanol injection (PEI) has been proposed for the therapy of autonomously functioning thyroid nodules. In 1992, an Italian multicenter study was undertaken to confirm the usefulness and the feasibility of this procedure. The study included 429 patients: 242 (56.4%) were affected by a toxic adenoma (TA) and 187 (43.5%) by pretoxic adenoma (PTA). Free thyroid hormone levels (FT4, FT3) and thyroid stimulating hormone (TSH) were measured before and 3, 6, 12 months after the end of treatment; thyroid ultrasound and thyroid scintiscan were performed in the majority of patients before and after treatment. Patients underwent 2-12 sessions of ethanol injection under sonographic guidance (median 4). The total amount of ethanol administered per patient (1.5 mL/mL nodular volume) was 2-50 mL (mean +/- SD, 17 +/- 9 mL), and the amount per each injection was 1-8 mL (3.2 +/- 1.3 mL). The treatment was judged successful when both TSH and free thyroid hormone serum levels returned within the normal range and recovery of tracer uptake in extranodular tissue was observed at scintiscan, at any time during the follow-up period. The treatment was considered unsuccessful when no change was observed at scintiscan and/or serum TSH levels remained less than 0.4 mU/L. A successful treatment was achieved in 66.5% of patients with TA and in 83.4% of patients with PTA, when assessed after a 12-month follow-up. In all cases a reduction of the nodular size was observed. Almost all positive results were obtained in nodules whose initial volume was less than 15 mL; large nodules responded less favorably. The treatment was generally well tolerated, only transient side-effects, mainly local pain at the time of injection, were observed. Once normalization of scintigraphic image and of FT4, FT3 and TSH serum concentrations was achieved, no recurrence of hyperthyroidism nor development of hypothyroidism were observed for the length of the study. In conclusion, percutaneous ethanol injection for treatment of autonomously functioning thyroid nodules is effective and safe. Better results are obtained in patients with PTA than in patients with TA, particularly when the initial volume of the nodule is less than or equal to 15 mL. PEI may be considered as an alternative to surgery and to radioiodine for treatment of autonomously functioning thyroid nodules.