The metabolic clearance rate of progesterone has been studied by single injection (MCRR) [2340 ± 183 (se) l/day in 7 subjects] and by continuous infusion (MCRr) methods in the third trimester of pregnancy in 22 normal women [2020 ± 135 (se) l/day], 10 women with abnormal intravenous glucose tolerance (GTT) [2830 ± 229 (se) l/day], and in 11 insulin-dependent diabetic women—7 treated with estrogen and progestin [2400 ± 176 (se) l/day] and 4 not treated with estrogen and progestin [2260 ± 280 (se) l/day]. The inner volume of distribution (VI) in normal pregnant women was 13.2 ± 1. 3 (se) 1 and the outer volume assuming metabolism in tie inner compartment to be zero VQa=0 was 38.0 ± 7.6 (se) 1 and assuming metabolism in the outer compartment to be zero VQe=0 was 21.0 ± 4.1 (se) 1. The plasma/blood concentration of 3H-progesterone was 1.55 (expected ratio 1.59), and therefore, progesterone is distributed primarily in the plasma during pregnancy. The MCRr for patients with abnormal GTT was different from normals (P < 0.005); however, when corrected for body surface area (BSA) there was no difference [1150 ± 75.5 (se) l/day/m2 in normal subjects, cf. 1380 ± 117 (se) l/day/m2 in abnormal GTT subjects]. There was no difference in the MCRr, therefore, among normal pregnant, pregnant with abnormal GTT, and insulin-dependent diabetic pregnant women treated or not treated with estrogen and progestin. The plasma progesterone concentration in 30 normals was 10.4 ± 4.27 (sd) μg/100 ml with a production rate (PI) of 210 ± 77.8 (sd) mg/day; in 10 patients with abnormal GTT 9.0 ± 3.12 (sd) μg/100 ml and PI of 248 ± 85.7 (sd) mg/day; and in 7 insulin-dependent diabetics receiving estrogen and progestin 11.2 ± 3.91 (sd) μ/100 ml with PI of 262 ± 84.8 (sd) mg/day, and in 4 insulin-dependent diabetics not receiving estrogen and progestin 13.5 ± 3.09 (sd) μg/100 ml with PI of 288 ± 77.8 (sd) mg/day.