Multicompartmental analysis of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) kinetics based on the plasma disappearance curves of the two tracer hormones (J. J. DiStefano III, M. Jang, T. K. Malone, and M. Broutman. Endocrinology 110: 198-213, 1982 and J. J. DiStefano III, T. K. Malone, and M. Jang. Endocrinology 111: 108-117, 1982) was extended to include additional experimental data, namely, the appearance curve in plasma of labeled T3 generated in vivo from precursor T4. Kinetic analysis of data obtained in 14 studies carried out in normal subjects by using a composite six-pool model made it possible to quantify the contributions of the thyroid (3.3 micrograms.day-1.m-2) and the periphery (12.7 micrograms.day-1.m-2) to T3 production. T4 monodeiodination occurred mainly in peripheral tissues rapidly exchanging with plasma (10.7 micrograms T3.day-1.m-2), whereas only 2.0 micrograms T3.day-1.m-2 arose in slowly exchanging tissues. In contrast, if plasma disappearance curves only were analyzed, a value of 10.9 micrograms T3.day-1.m-2 was calculated for peripheral conversion in slowly exchanging tissues; this underscores the need for additional data, such as the [125I]T3 plasma appearance curve for the partition of central and peripheral production of T3.