Five fasting women had a steady-state concentration of progesterone (P) established by a constant intravenous infusion of P during the early proliferative phase of a spontaneous menstrual cycle. Alterations in the levels of P after the ingestion of a balanced liquid meal were sought. Eight studies were performed utilizing the five women. P levels decreased in all observations; the mean (+/- SE) decrease was 34.2 +/- 0.2% 60 minutes after the meal (p = 0.0001). By contrast, mean cortisol (F) levels increased 29.5 +/- 14.4% (p = 0.11) 60 minutes after the meal and postprandial F levels were variable both within and between individuals. The correlation between the change in P and F, 60 minutes after the meal, was not significant (r2 = 0.015, p = 0.77). These findings indicate that: 1) The postprandial state is associated with a transient and large increase in the metabolic clearance rate of P and/or a change in the volume of distribution of P and 2) Increased F levels after meals alone do not appear to account for a postprandial decrease in P.