Aspects of 3,5,3′-triiodo-l-thyronine (T3) metabolism were studied in fed rainbow trout (Oncorhynchus mykiss) held at 11.5-14° and intraperitoneally implanted with hydrogenated corn oil (controls) or oil containing cortisol. Cortisol implants caused dose-related plasma cortisol elevations within the physiological range for 2-3 weeks, loss in body weight, and depression in plasma T3 and free T3 index with no consistent change in plasma thyroxine (T4) or free T4 index. Plasma T3 clearance rate and plasma T3 appearance rate were both increased by cortisol, with no change in hepatic microsomal T4 5′-monodeiodinase activity (Km or Vmax), but with a significant decrease in muscle T3 concentration. It is concluded that chronic physiologic cortisol treatment enhances plasma T3 clearance without change in hepatic T4 to T3 conversion, resulting in a decline in T3 concentration in both plasma and tissue (muscle) compartments. © 1991.