An isotopic equilibrium method was employed, based on the chronic feeding of an 125I-labeled diet of known specific activity, to determine the distribution and quantitation of endogenously labeled iodine-containing compounds in the female rat at various periods during gestation and post-parturition. A decrease was associated with gestation in the total iodine, which was significant in all extrathyroidal tissues except the brain and muscle, and a fall in thyroxine concentration which was significant in all extrathyroidal tissues except the heart. The triiodothyronine level decreased from the control values in gestation but not as consistently. There was also a significant decrease in the total iodine and thyroxine in the plasma at this time. Concomitant with this fall in plasma iodinated compounds was a significant increase in the free thyroxine percentage. These changes were paralleled by an increased renal and fecal excretion of iodide. Total iodine, T4, T3, MIT and DIT all increased in the thyroid gland; however, these changes in the latter 3 compounds were statistically insignificant. These findings indicate that during gestation the body stores of iodinated compounds become depleted with the exception of the thyroid, which shows a greater than normal absolute concentration. A postulated increased T4 turnover rate, which could be due to a high maternal deiodination or placental thyroxine permeability and fetal deiodination, could account for the above observations. Following parturition, there was an excessive rebound of the iodinated compounds over an approximate 4 week period towards control values. In the lactating rat, these compounds remained below non-lactating levels until after weaning and then returned to the control levels rapidly. The total iodine levels in the plasma were extremely low during lactation and rose slowly as milk secretion decreased. These postpartum observations were for the most part statistically insignificant although they revealed a definite trend. These low levels of total iodine could be explained by the secretion of iodide by the mammary gland during lactation. There was an increased accumulation of total iodine, T4, T3, MIT and DIT by the thyroid gland during lactation. These data suggest an adaptation of the thyroid to the increased need for T4 to support or control the mammary glands.