The relationship between the changes in thyroglobulin (Tg) mRNA and Tg proteins during thyroid development in the fetus and in maternal thyroid glands during gestation and lactation is studied. While the appearance of Tg mRNA (fetal day 15) showed good temporal correlation with that of 12S Tg, no 19S Tg could be detected until 3 days later. The 12S Tg was the predominant protein on days 18 and 19 of gestation in the fetus, while 19S Tg was the predominant protein on fetal days 21-22 and during the postnatal period in the offspring; by the 20th postnatal day, the 19S Tg content per gland was 4 times the amount of 12S (155 vs. 37 micrograms/gland; P less than 0.001). The 19S iodine content in the fetus was the same as that in 12S up to the 21st day of gestation, except for lower values on day 18. From fetal day 22 and through the postnatal period, the iodine content in 19S was 1.6-5.9 times greater than that in 12S. Therefore, the ratio of atoms of iodine per mol Tg during the experimental period changed from 0.75 to 19.5 for 19S and from 0.72 to 7.2 for 12S. The levels of all of the iodoamino acids were low on fetal days 17-19, after which they increased at different rates for each protein. The greatest increase in monoiodotyrosine and T3 corresponded to 12S, while diiodotyrosine and especially T4 showed a greater increase in 19S than in 12S Tg; 20 days after birth, the T4 content in 19S was about 3 times greater than that in 12S Tg. The soluble thyroid proteins from pregnant, lactating, and nonpregnant female controls contained a main protein, 19S, and a smaller amount of 27S. Both 19S Tg and 19S iodine contents were already lower than those in nonpregnant rats at 14 days of pregnancy, and the levels continued to decrease during the experimental period. In contrast, the 27S Tg and 27S iodine levels remained constant and similar to nonpregnant values. Surprisingly, a decrease in the level of Tg mRNA was observed during pregnancy and lactation. We have no explanation for the dramatic decrease in Tg mRNA during the last days of pregnancy. Further studies should help to elucidate the mechanism responsible for the changes in Tg gene expression in the thyroids of pregnant and lactating rats.