Sixty patients with Graves' disease (GD) hyperthyroidism were distributed in two randomized groups. Patients in group A (n = 30) received carbimazole by a titration regimen, and patients in group B (n = 30) were treated with higher doses of carbimazole plus T4. Clinical and analytical evaluations were done at baseline, during treatment (18.4 +/- 2.6 months), and after, until the relapse of hyperthyroidism, or for 4.98 +/- 1.6 yr in patients who did not relapse. There were no differences in clinical parameters, thyroid hormones, or TSH binding inhibitory immunoglobulins (TBII) levels between the two groups, either at baseline or at the end of treatment. Serum TSH persisted undetectable in 16 out of 60 patients (group A: 9; group B: 7), after treatment. Relapse occurred in 38 patients (63.3%), (group A: 18 (60%) vs. group B: 20 (66.7%)). Patients who relapsed had bigger goiters at baseline (P = 0.02) and at the end of treatment (P = 0.03). Eighty-seven percent (14/16) of patients with undetectable TSH after therapy relapsed, vs. 54.5% (24/44) of those with normal TSH (P = 0.01). Undetectable TSH at the end of treatment was the only independent variable in the logistic analysis to predict relapse. Treatment modality did not influence the relapse rate. This study has found that, in Spanish patients, the use of high doses of carbimazole with T4 offers no advantages in the treatment of GD hyperthyroidism.