The ontogeny of the fetal monodeiodinase systems, during the period before the onset of thyroid activity until birth, has been described only in the rat, rabbit and chick. We have studied 5'- and 5-monodeiodinase activities in the liver, kidney and placenta of pig fetuses, from day 32 of gestation up to birth, and on days 1, 3, 7 and 14 after birth. Fetuses (123) from 15 litters, 32 newborn piglets, 15 sows (mothers) and 10 non-pregnant pigs were used. The relationships between monodeiodinase activities, thyroxine (T-4), tri-iodothyronine (T-3) and reverse tri-iodothyronine (rT(3)) blood serum concentrations and sulphydryl groups (total (T-SH) and non-protein (NP-SH), were measured. 5'-Monodeiodinase activity (5'-MD type I; converting T-4 to T-3) and 5-monodeiodinase (5-MD; converting T-4 to rT(3)) were detectable in the liver at the onset of thyroid hormone biosynthesis, and before that time (day 32 of gestation) in the placenta. Liver 5'-MD activity was very low between days 32 and 84 of gestation, and then increased rapidly at about day 93, reaching a maximal value 2 days before term. Activity in the liver (but not in the kidney) was higher than that in maternal, newborn and non-pregnant adult tissue. The increase in NP-SH groups in the liver and kidney and T-SH groups in the placenta during the last 5 days of gestation coincided with the increase in 5'-MD activity. The 5-MD activity of the liver was generally five to ten times lower than that of 5'-MD, being highest on days 65-76 and 65-84 in the kidney and placenta respectively. Serum T-4 concentrations paralleled the steady increase in T-4- to T-3-converting activity in the kidney and liver, but not in the placenta. Two weeks before birth, fetal T-3 concentrations exceeded those of rT(3) by a factor of 1.5 or more, indicating that T-4 metabolism in the pig is dominated by the activity of 5'-MD. This pattern is different from that in prenatal humans, rats or sheep in which rT(3) is the primary circulating T-4 metabolite.