Objective Abnormalities in thyroid state may affect development and function of the brain and result in mental retardation (MR). Thyroid parameters have not been systematically investigated in institutionalized MR subjects. The objective is to measure thyroid parameters in a novel cohort of 946 institutionalized subjects. Design The TOP-R (Thyroid Origin of Psychomotor Retardation) study is a cross-sectional nation-wide multicentre study. Patients Subjects with unexplained MR. Results The majority of the MR subjects had thyroid parameters within the reference range used in our laboratory. Antiepileptic drugs (AEDs) use affected thyroid hormones (T4: 102.1 +/- 1.2 vs 83 9 +/- 1 2 nmol/l, P < 1 x 10(-24); FT4: 18.0 +/- 0.2 vs 16.1 +/- 0.2 pmol/l, P < 1 x 10(-9); T3: 1.72 +/- 0.02 vs 1.57 +/- 0.02 nmol/l, P < 1 x 10(-9); and rT3: 0.37 +/- 0.01 vs 0.27 +/- 0.01 nmol/l, P < 1 x 10(-28) in subjects without vs with AEDs). The prevalence of unrecognized primary hypothyroidism and hyperthyroidism was 5.2% and 2.8%, respectively. Conclusions We report thyroid parameters in a cohort of institutionalized subjects with MR. Our findings substantiate the fact that AEDs affect thyroid hormone levels. Future studies will be employed to investigate genetic causes of MR related to abnormalities in thyroid hormone homeostasis.