Differences in blood levels of thyroid hormones have been reported when patients taking synthetic L-thyroxine were shifted from one manufactured form of the hormone to another. Because recent formulation changes have rendered these earlier data obsolete, we did a crossover study to determine differences in bioavailability of the two principal brands of thyroxine, Synthroid and Levothroid. Twenty patients received Synthroid and then Levothroid, and 14 received Levothroid and then Synthroid. Patients received each drug for 6 weeks. Although no significant differences were seen in routine thyroid hormone measurements, combined data from both groups showed a significantly higher free thyroxine level in the patients treated with Synthroid, as well as lower thyrotrophin values at 15 and 30 minutes after administration of thyrotrophin-releasing hormone. Equal doses of the currently manufactured forms of these two products are similar but not bioequivalent.