Twenty autonomously functioning thyroid nodules were treated with ultrasound-guided percutaneous ethanol injection (PEI) and followed for 12 months. PEI was performed on symptomatic and biochemically proven thyrotoxic patients by injecting 2.0-4.0 mL sterile ethanol and was repeated 3-8 times, depending on nodule size. Serum thyroglobulin increased immediately after PEI, peaked at 6-10 h, and declined thereafter. Free T4 progressed slowly during the first 24 h. Free T3 showed a delayed and not significant increase. By the end of the treatment (4 weeks), PEI had produced clinical improvement and hormonal normalization. Three months later, serum TSH was detectable and responsive to TRH in 17 of the 20 patients. All nodules had a significant shrinkage at ultrasound evaluation. The previous hot thyroid areas manifested hypofunction at technetium-99 m-pertechnetate scintiscan, and the surrounding parenchyma returned to normal function in all but the 3 cases with still suppressed TSH. The histological features of a nodule that had been operated upon and the fine needle aspiration biopsy patterns obtained after PEI showed coagulative necrosis, with scanty follicles, some fibroblasts, but no lymphocytic infiltration. The procedure was generally well tolerated, but in 1 case it induced temporary dysphonia, and in another patient, it caused a transient exacerbation of thyrotoxicosis.