OBJECTIVE The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism.DESIGN Prospective open multicentre trial.PATIENTS Sixty‐three patients presenting with hyperthyroidism.MEASUREMENTS Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks.RESULTS Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 ± 10it158 ± 11 nmol/l,P < 0.001) and free T4 (19.4 ± 2.6vs35.2 ± 3.7 pmol/l,P < 0.001) and total (2.6 ± 0.3vs4.3 ± 0.4 nmol/l,P < 0.001 and free T3 (8.3 ± 1.0vs13.7 ± 1.2 pmol/l,P  260 nmol/l.CONCLUSIONS In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with