Thyroid hormone levels and beta-adrenergic responsiveness after stimulation with the beta-adrenergic agonist isoproterenol were studied in four groups of male rats. The groups used were control rats, rats deprived of food for 72 h, rats administered 50 micrograms thyroxine (T4)/kg daily for 4 days, and rats deprived of food for 72 h and administered 50 micrograms T4/kg daily for 4 days. Food deprivation significantly decreased serum T4 and triiodothyronine (T3) levels, and administration of T4 significantly increased serum T4 and T3 levels in both fed and food-deprived rats. Administration of T4 led to lower body weights in both fed and food-deprived rats. Administration of isoproterenol led to increases in colonic and tail skin temperatures and heart rate. Food deprivation significantly attenuated the increased body temperatures and heart rate induced by isoproterenol, and administration of T4 to food-deprived rats returned these adrenergic responses to control levels. Administration of T4 to fed rats significantly increased the thermal and cardiac responses to isoproterenol above those of the control rats. Administration of isoproterenol also increased plasma glucose levels. Food deprivation significantly decreased both postsaline- and isoproterenol-stimulated glucose levels. However, administration of T4 was without effect on either the postsaline- or isoproterenol-stimulated glucose levels of either the fed or food-deprived rats. The decreases in T4 and T3 that accompany food deprivation may thus be responsible for some, but not all, of the reductions in beta-adrenergic responsiveness observed in food-deprived rats.