A Cortland saline-perfused rainbow trout (Oncorhynchus mykiss) liver model was used to study aspects of T 4 efflux from the intact organ system. There was a consistent efflux of T 4 in the absence of T 4 in the perfusate, and the T 4 efflux was increased in the presence of T 4 in the perfusate, but the efflux was not T 4 -dose dependent. The addition of the thiol-containing compound dithiothreitol (DTT, 2 mM) to the perfusate had no significant effect on the flux of T 4 from the liver, whereas the addition of cysteine (2 mM), a thiol-containing amino acid suppressed T 4 efflux. The results are consistent with the known mechanisms of thyroid hormone trafficking across cell membranes, and suggest that organ systems, such as the liver, may act as a major reserve of hormone, thus participating in plasma thyroid hormone homeostasis.