Maternal plasma unconjugated estriol (E3), progesterone (P), and estradiol (E2) levels were measured at 30-min intervals for 6 h after the rectal administration of a 100-mg E3 or placebo suppository to 28 pregnant women at term. Mean plasma unconjugated E3 levels showed a sustained rise approximately 50% above baseline levels 2 h after rectal E3 administration (P < 0.003). There was a simultaneous sustained fall of approximately 20% in mean plasma P levels (P < 0.05); the fall in mean P levels was greatest in the women who delivered within 48 h of E3 suppository administration (P < 0.05). There was no change in mean plasma E2 levels. This study demonstrates that a significant rapid increase in maternal circulating E3 levels can be obtained by the rectal administration of E3, and that this increase in maternal E3 levels is associated with a decrease in circulating P levels.