Thyroxine replacement therapy for 21 adult patients with primary hypothyroidism was adjusted to the dosage at which each patient had a normal thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH). Clinical assessment and measurement of TSH (by sensitive immunoradiometric assay), free thyroxine (FT4) and free tri-iodothyronine (FT3) were made at this dosage and at higher and lower doses of thyroxine. Clinical observations, FT3 and FT4 assays were relatively insensitive to small alterations of thyroxine dosage, in contrast to which basal TSH measurements correlated well with TRH responsiveness and were sensitive to fine adjustments of thyroxine dosage.