Tracer thyroxine (T4), 3.3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) kinetic studies were performed in normal T4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. T4 plasma appearance rate decreased by 16% (P less than 0.01), reflecting a decreased intestinal absorption of orally administered T4 during propranolol. Serum T4 and free T4 levels increased significantly by 14%, whereas T4 metabolic clearance rate (MCR) was lowered by 26% (P less than 0.001). No changes were observed in size of the three T4 compartments or in fractional and mass transfer rates of T4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T3, free T3, T3 plasma pool, T3 mass transfer rate to REP and SEP, and the T3 pool masses were all significantly decreased during propranolol to a similar extent as the T3 plasma production rate (PR). T3 MCR decreased by 14% (P less than 0.05). Serum total and free rT3 increased, whereas the rT3 MCR was substantially lowered during propranolol (P less than 0.001). The rT3 plasma pool, rT3 REP and SEP, and the mass transfer rates to REP and SEP increased, whereas no alterations were observed in rT3 PR and fractional transfer rates of rT3 to REP and SEP.(ABSTRACT TRUNCATED AT 250 WORDS)