In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T₃) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T₃ nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TRα and TRβ) and retinoid (RARα, RARγ, and RXRα) nuclear receptors in PBMC of euthyroid (n=22) compared with hypothyroid (n=22) subjects. Classical plasma parameters (free T₃ (FT₃), free thyroxine (T₄) (FT₄), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T₃ and T₄ concentrations were associated with a decrease in the expression of TRβ. Expression of RARα and RARγ significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.