Clinically euthyroid patients on long term maintenance therapy with the non-steroidal anti-inflammatory drug fenclofenac (Flenac) show an unusual and abnormal pattern of serum thyroid function tests. In all twelve patients studied, total T4 concentrations were grossly subnormal (mean 28.4 +/- 9.9 (SD) nmol/l and total T3 levels low-normal (mean 1.4 +/- 0.3 (SD) nmol/l), whereas rT3 (mean 0.36 +/- 0.06 (SD) nmol/l) and basal TSH levels (mean 1.9 +/- 0.5 (SD) mu/l) were within their respective normal ranges. Free T4 levels were low normal (mean 11.0 +/- 1.0 (SD) pmol/l) while TSH, T4 and T3 responses to intravenous TRH were similar to those found in euthyroid subjects. These effects appear to be due predominantly to in vivo inhibition of binding of thyroid hormones to carrier proteins in serum, rather than in vitro drug interference in the radioimmunoassays employed. Fenclofenac does, however, interfere in those laboratory methods employing serum proteins as binding agents. Thus the Thyopac 4 method for serum total T4 grossly over-estimates T4 levels, while thyroid hormone binding capacity (Thyopac 3) is low. Since fenclofenac is one of the most potent drugs interfering with routine indices of thyroid status, it is suggested that suspected thyroid dysfunction is excluded before commencing therapy with the drug.