BACKGROUND Pretreatment thyrotropin levels may be a reliable predictor of the optimal daily dose of levothyroxine sodium in patients with primary hypothyroidism. However, the older method of serum thyrotropin determination, with the reference range of less than 1 to 8 mU/L, has given way to a newer, supersensitive thyrotropin assay, with a reference range of 0.5 to 5.0 mU/L. Thus, at present, the previously established relationship between the levothyroxine dose and the pretreatment serum thyrotropin concentration may not be reliable in predicting the optimal daily dose of levothyroxine. METHODS We reassessed the relationship between the optimal daily levothyroxine dose and the pretreatment serum thyrotropin concentration as determined by the newer assay in 192 consecutive patients with primary hypothyroidism referred to an endocrinology clinic over a period of 4 years. RESULTS The optimal daily dose of levothyroxine sodium ranged from 25 to 225 micrograms, with most patients (65%) requiring 100 to 150 micrograms/d and a median dose of 125 micrograms. Multiple regression analysis documented a significant curvilinear correlation between the mean pretreatment serum thryrotropin concentration and the optimal daily levothyroxine dose for individual groups divided according to available tablet strengths (r = .994, P < .001). A simple linear regression was also significant (r = .92, P < .001), although with an intercept much higher than the minimum levothyroxine sodium dose of 25 micrograms/d. However, the relationships markedly improved when the linear regressions were determined separately for two further subgroups at the median daily dose of 125 micrograms, providing equations to predict even the smallest optimal daily dose of levothyroxine. CONCLUSIONS Pretreatment thyrotropin levels determined by new assays may also provide a useful guideline in determining the optimal daily maintenance dose of levothyroxine in patients with primary hypothyroidism.