There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (I-131) therapy in Graves' disease by reducing the absorbed energy dose of I-131 when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative I-131 therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200-250 Gy. We prospectively studied 207 patients with Graves' disease (106 with and 101 without simultaneous carbimazole at the time of I-131 therapy). All patients were reexamined 3, 6, and 12 months after I-131 therapy. The 101 nonthyrostatic patients showed a highly sig nificantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during I-131 therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related to free T-3, free T-4, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs, r = 0.24). Sixteen patients who discontinued thyrostasis 1-3 days before I-131 therapy showed 94% successes. Simultaneous thyrostasis is the decisive factor against a successful I-131 therapy even if the significantly reduced I-131 uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning I-131 therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.