The effects of cadmium on 5′-deiodination of thyroxine (T4) by rat liver and on the hepatic concentration of non-protein sulfhydryl groups (NPSH) were studied in Wistar rats of 200–250 g body weight. A group of ten rats was injected with cadmium chloride (300 μg/100 g body weight i.p.) daily for 4 days. Another group of six rats received, in addition, dithiothreitol (DTT; 1 mg/100 g body weight i.p.) daily for the same period. A group of eight normal untreated rats served as control. T4 deiodination was also determined in aliquots of liver from untreated rats, with cadmium (2 or 5 mmol/l) and with or without DTT (0, 2·5, 5 or 10 mmol/l) plus 1 μCi 125I-labelled T4. Hepatic NPSH were measured by a colorimetric method employing dithioldinitrobenzoic acid. Homogenates were incubated for 90 min at 37 °C and chromatographed in a tertiary amyl alcohol: hexane: ammonia (2 mol/l) (10: 1: 12) system. Cadmium-injected rats showed a significant (P <0·01) decrease in T4 deiodination and in the generation of 125I (P <0·01) and tri-iodothyronine (T3) (P <0·02). NPSH were also decreased (P <0·02). Administration of DTT restored T4 deiodination and NPSH to normal. In-vitro addition of cadmium or DTT to normal rat liver homogenates induced similar effects on the degradation of T4. Serum concentrations of T4 (P <0·01) and T3 (P <0·01) declined significantly in cadmium-injected rats, whereas DTT administration failed to normalize serum hormone levels. The data suggest that cadmium may have decreased 5′-deiodinating activity through binding to sulfhydryl groups of 5′-deiodinase as it does in other enzymes. The effects on serum T4 concentrations may be unrelated to those on 5′-deiodinase.