Various methods were employed to detect changes in the peripheral degradation of thyroxine (T4) in adult Uinta ground squirrels (Citellus armatus) collected at two different altitudes (5400 and 9000 feet.) Plasma half-life of injected T4-125I (tl/2) was significantly decreased with altitude, as was T4-125I distribution space (TDS) and T4 degradation and secretion rate (TSR). In vitro deiodination of T4-125I by heart homogenates was not affected, while urinary excretion of thyroxine derived iodide was increased at high altitude 44-70 hours post-injection. Both total and free serum T4 concentrations were reduced at high altitude, although not significantly. The cause of the reduced tl/2 at high altitude was not evident, while the decreased TDS was probably due to a reduced plasma volume. Increased urinary and fecal clearance could account for the decreased total and free serum T4. TSR was reduced due to the low TDS and T4 concentration observed in high altitude squirrels.