The mechanisms that are responsible for the extension of lifespan In the mouse with targeted disruption (knockout [KO]) of the growth hormone (GH) receptorlblnding protein (GHR-KO) are unknown. However, In the long-living Ames dwarf mouse, blood glucose and body core temperature (Teo) are consistently lower than In normal mice. In addition, Insulin levels are reduced and corticosterone levels are elevated In male dwarfs. These functional alterations, similar to those seen In animals under caloric restriction, have not been proven to be causally related to the extension of lifespan, but they do provide some Insight Into what traits may be necessary tor long life. Therefore, to Investigate which of these parameters are similarly affected In two genetically unrelated, yet similarly long-living mouse models, we measured Teo' thyroid hormones (trIIodothyronine [T3Jand thyroxine [T4])' and Insulin, In addition to mornIng and afternoon levels of glucose and corticosterone, In young adult male and/or temale GHR-KOmice and their normal siblings. Teo In GHR-KOmice was numerically reduced throughout the 24-hr period; however, these differences were only significant 4 hr prior to lights-off (14:00 hr), Immediately after lights-off (18:00 hr), and during the 3 hr preceding lights on (03:00 to 06:00 hr). GHR-KO mice had significantly reduced levels of T 3 and T 4 , while the ratio of these hormones was similar to that In normal mice. Insulin levels In GHR-KO mice were lower than In normal mice; levels In male GHR-KO mice were below the detectable limits of the assay used. Glucose levels In GHR-KO mice (male and females) were lower than In normal mice In measurements taken In both morning and afternoon; however, these differences arose from consistent reductions In