The relative bioavailability and therapeutic equivalence of two brands of levothyroxine sodium tablets, Levothroid and Synthroid, were compared in patients who had been receiving long-term levothyroxine replacement therapy. Eighteen patients with primary hypothyroidism were randomly assigned to receive therapeutic dosages of Levothroid or Synthroid for 43 days and then were switched to the opposite product for 43 more days. The pharmacokinetic profiles of the two drugs were evaluated on days 43 and 86 by analyzing blood samples drawn at various intervals after the final dose. Relative bioavailability was determined by comparing the absorption profiles and areas under the serum concentration-time curves (AUCs) of total and free serum thyroxine. In addition, the potency of the levothyroxine sodium tablets was determined by high-performance liquid chromatography. The time to reach maximum concentration and the maximum concentration of total thyroxine after treatment with Levothroid did not differ significantly from those after treatment with Synthroid. The mean +/- S.D. AUC of total thyroxine after Levothroid administration (2339 +/- 404 pg.hr/mL) was slightly but significantly higher (p = 0.047) than that following Synthroid (2169 +/- 422 pg.hr/mL). However, the main index of biological activity, thyrotropin concentration, did not differ significantly between the two products. All tablets tested were within the stated potency requirements of the USP. The AUC of total serum thyroxine and the serum thyrotropin concentration after long-term replacement therapy with Levothroid or Synthroid indicate that any differences in bioavailability between the two products are clinically unimportant and that the two products are therapeutically interchangeable.