OBJECTIVE: The long-term effects of (131)I-therapy in patients with symptomatic non-toxic diffuse goitre were evaluated. DESIGN AND METHODS: In a prospective open study, 34 patients (median age: 40 yrs, range: 27-68 yrs) were enrolled who suffered from a non-toxic goitre absent of nodules on clinical examination and on ultrasonography. Treatment indication was the presence of goitre giving rise to cervical compression and/or cosmetic discomfort. The median (131)I activity was 600 MBq (200-600 MBq) administered orally on an outpatient basis. The patients were investigated by clinical examination, thyroid ultrasonography and thyroid function tests at regular intervals and for at least 12 months after the (131)I-therapy. Yearly follow-up continued until the end of the study period or if permanent hypothyroidism ensued. The severity of symptoms was evaluated by a Visual Analogue Scale (VAS) (range: 0-10). RESULTS: The median follow-up time was 36 months (12-84). Goitre volume was reduced from 67.9+/-28.5 ml to 43.4+/-18.7 ml (mean+/-S.D.) (P<0.001) 3 months after the (131)I-therapy. After 3 years of follow-up, only 28.1+/-2.0% (mean+/-S.E.) remained of the initial goitre mass (P<0.001). Goitre was no longer present in 76% of the patients at the end of follow-up. An inverse correlation was found 1 year after therapy, but not after 3 years, between the initial goitre size and the percent reduction (r=-0.44, P=0.01). Thirty-six percent had become hypothyroid after three years. Median VAS scores were reduced from an initial 7.0 (cervical compression) and 5.5 (cosmetic discomfort) to 0.0 at the end of follow-up (P<0.001). CONCLUSION: Our data justify treatment of non-toxic diffuse goitre with (131)I because goitre reduction is pronounced, along with a very high degree of patient satisfaction and few side effects. We suggest that (131)I-therapy can be used as an alternative to L-T(4) suppressive therapy and thyroidectomy in this group of patients.