Context: Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side-effects are dose-dependent. Objective: To determine the effects on thyroid size and function of various doses of rhTSH. Design: In nine healthy male volunteers the effect of placebo, 0.1, 0.3 and 0.9 mg of rhTSH was examined in a paired design including four consecutive study rounds. Main outcome measures: Were evaluated at baseline, 24h, 48h, 96h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, freeT3, freeT4 and Tg levels. Results: Following placebo or 0.1 mg rhTSH the TV did not change significantly from baseline at any time. At 24 and 48 hours after administration of 0.3 mg rhTSH TV increased by 37.4+/-12.3(SEM)% (p=0.03) and 45.3+/-16.1% (p=0.05), respectively. After 0.9 mg rhTSH TV increased by 23.3+/-5.8% (p=0.008) and 35.5+/-18.4% (p=0.02), respectively. The increase in serum FT3, FT4, and thyroglobulin (Tg) was greater when administering 0.3 mg compared to 0.1 mg (p=0.02) and when administering 0.9 mg compared to 0.3 mg (p=0.02). After 0.1 mg rhTSH the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (p=0.02 compared to placebo). Conclusions: In healthy individuals rhTSH-induced thyroid swelling and hyperthyroidism is rapid and dose-dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0.1 mg or less.