Near term in the rat, the blood concentration of progesterone falls while that of 20 alpha-hydroxypregn-4-en-3-one (20 alpha-DHP) increases. This is generally attributed to changes in ovarian secretion alone, but altered rates of hormone metabolism could also have a role. In the present study, therefore, metabolic clearance rate (MCR), production rate, and peripheral interconversion of progesterone and 20 alpha-DHP were measured on Day 16 of pregnancy, the time of maximal progesterone secretion, and on Day 22, one day prior to parturition. Conscious rats (n = 8 per group) were infused with either [3H]progesterone or [3H]20 alpha-DHP and the dynamics of progestin metabolism were calculated from the resultant isotopic and endogenous progesterone and 20 alpha-DHP concentrations. The blood concentration of progesterone declined by 69% between Day 16 (54 +/- 2 ng/ml) and Day 22 (17 +/- 2 ng/ml), and this was due to the combined effect of a 48% increase in the MCR and a 54% decrease in production rate of progesterone. In contrast, the production rate of 20 alpha-DHP was twofold greater on Day 22 compared to Day 16. As a result, the blood concentration of 20 alpha-DHP increased from 28 +/- 3 ng/ml on Day 16 to 40 +/- 6 ng/ml on Day 22, and this change would have been greater but for a concomitant increase (41%) in the MCR of 20 alpha-DHP. Although peripheral conversion of progesterone to 20 alpha-DHP was similar on Day 16 (transfer constant, 12.8 +/- 0.6%) and Day 22 (12.3 +/- 0.9%), the contribution of this conversion to total 20 alpha-DHP production fell from 32% to 7% between the two days.(ABSTRACT TRUNCATED AT 250 WORDS)