Objective: For patients who remain hypothyroid despite the administration of what would seem adequate doses of levothyroxine (L-T 4 ), the underlying cause can be difficult to determine. The possibility of a biological cause should first be explored; however, in the majority of cases, poor adherence to medication is likely to be the main cause of treatment failure. When non-adherence is suspected but not volunteered, options to confirm the suspicion are limited. In this study, we identified patients for whom known drugs and pathological causes of L-T 4 malabsorption were excluded, and despite often high doses of L-T 4 , the patients remained hypothyroid. Design: Using a weight-determined oral L-T 4 bolus administration, absorption was initially assessed in 23 patients. In nearly all patients, this was shown to be maximal at 120 min post-ingestion. This was then followed by the continued administration of a weekly T 4 bolus for a 4-week period after which TSH and free T 4 (fT 4 ) levels were recorded. Results: All patients showed a rise in fT 4 at 120 min following the administration of the L-T 4 bolus, with a mean increase of 54G3% from baseline. Following the treatment period, using an equivalent weekly L-T 4 dose, which was significantly less than that of the daily dose taken by the patients before the test, TSH reduced from baseline in w75% of cases. Conclusion: Using this combination of tests allows significant malabsorptive problems to be identified first and then potential non-adherence to be demonstrated. A management plan can then be implemented to increase adherence, aiming to improve treatment outcomes.European Journal of Endocrinology 168 913-917