The liver and kidney nuclear T3 content and the maximal nuclear T3-binding capacity (MBC) were measured 1 month after streptozotocin administration and compared with values in controls either fed ad libitum (C) or offered a restricted diet (FR). A group of insulin-treated diabetic (D+I) rats was also included. Plasma T4 and T3 concentrations decreased to low levels in diabetic (D) rats. Plasma T3 levels were decreased in FR rats, whereas circulating T4 was in the normal range for C animals. The MBC (nanograms of T3 per mg DNA) for liver and kidney nuclear T3 was determined by an in vivo saturation technique. The respective results for all groups were as follows (asterisks denote values differing from C with P values less than 0.05): C, 0.601 and 0.414; FR, 0.583 and 0.369; D, 0.310 and 0.220; D+I, 0.630 and 0.394. Nuclear T4 and T3 concentrations were determined by an isotopic equilibrium technique. Nuclear T3 (nanograms per mg DNA) for liver and kidney were, respectively, 0.298 and 0.176 for C, 0.208 and 0.135 for FR, 0.109 and 0.070 for D, and 0.270 and 0.168 for D+I rats. The decreased liver and kidney nuclear T3 content in D rats appears to be due to a marked reduction of their available intracellular T4 pool, from which T3 could be generated, but most likely represents a decreased T3 uptake into liver and kidney nuclei, as the nuclear to plasma ratios of labeled T3 were decreased in D rats. The low levels of T3 in nuclei of FR rats could be attributed to an inhibition of T4 to T3 conversion, since the intracellular pool of T4 appears to be normal. The possibility that diabetes and food restriction might affect the thyroid activity was examined by measurement of the activities of alpha-glycerophosphate dehydrogenase and cytosol malic enzyme, two liver and kidney enzymes regulated by thyroid hormone. Furthermore, although the measurements made in FR rats excluded the possibility that the alterations in MBC found in D animals were nutrition dependent, the reduced nuclear T3 content concomitant with food restriction may account for some of the quantitative changes in the alpha-glycerophosphate dehydrogenase and cytosol malic enzyme activity found in D rat tissues. In conclusion, the present findings suggest that the observed changes in indices of thyroid hormone action in liver and kidney of D rats could be related to alterations in nuclear T3 receptor concentrations and the concentration of T3 bound to the receptor.