Objective: To examine the effect of combined lithium and divalproex sodium on thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorders and to identify risk factors for lithium-induced hypothyroidism. Method: Bipolar youths aged 5 to 17 years participating in an open-label clinical trial received treatment with lithium and divalproex sodium for up to 20 weeks. TSH levels were measured at baseline and at the end of the study. Subjects were divided into two groups for analysis: group 1 had TSH levels of less than 10.0 mU/L at the end of the study and group 2 had TSH levels of 10.0 mU/L or more at end of the study. Results: Twenty of the 82 subjects (24.4%) showed TSH elevations of at least 10 mU/L within an average exposure of less than 3 months. The mean baseline TSH level for group 2 was significantly higher than for group 1 (2.97 [SD = 1.48] versus 2.05 [SD = 0.89], p < .05). Mean lithium levels at the end of the study were 1.00 mEq/L for group 2 compared to 0.76 mEq/L for group 1 (t = -2.41, p = .019). Conclusions: Lithium is associated with significant rates of thyrotropin elevation in bipolar youths. Factors associated with elevation in TSH in lithium-treated subjects include a higher baseline TSH level and a higher lithium level. Close monitoring of thyroid function in children and adolescents taking lithium is recommended.