Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential for blood pressure and fluid regulation. We tested the hypotheses that combined progesterone (P4)-estrogen (E2) administration would increase ECF volume with proportional increases in PV, but that P4would have little independent effect on either PV or ECF volume. We further hypothesized that this P4-E2-induced fluid expansion would be a function of renin-angiotensin-aldosterone system stimulation. We suppressed P4and E2with a gonadotropin-releasing hormone (GnRH) antagonist in eight women (25 ± 2 yr) for 16 days; P4(200 mg/day) was added for days 5–16 (P4) and 17β-estradiol (2 × 0.1 mg/day patches) for days 13–16 (P4-E2). On days 2 (GnRH antagonist), 9 (P4), and 16 (P4-E2), we estimated ECF and PV. To determine the rate of protein and thus water movement across the ECF, we also measured transcapillary escape rate of albumin. In P4, [Formula: see text] increased from 2.5 ± 1.3 to 12.0 ± 2.8 ng/ml ( P < 0.05) with no change in [Formula: see text] (21.5 ± 9.4 to 8.6 ± 2.0 pg/ml). In P4-E2, plasma concentration of P4remained elevated (11.3 ± 2.7 ng/ml) and plasma concentration of E2increased to 254.1 ± 52.7 pg/ml ( P < 0.05). PV increased during P4(46.6 ± 2.5 ml/kg) and P4-E2(48.4 ± 3.9 ml/kg) compared with GnRH antagonist (43.3 ± 3.2 ml/kg; P < 0.05), as did ECF (206 ± 19, 244 ± 25, and 239 ± 27 ml/kg for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05). Transcapillary escape rate of albumin was lowest during P4-E2(5.8 ± 1.3, 3.5 ± 1.7, and 2.2 ± 0.4%/h for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05). Serum aldosterone increased during P4and P4-E2compared with GnRH antagonist (79 ± 17, 127 ± 13, and 171 ± 25 pg/ml for GnRH antagonist, P4, and P4-E2, respectively; P < 0.05), but plasma renin activity and plasma concentration of ANG II were only increased by P4-E2. This study is the first to isolate P4effects on ECF; however, the mechanisms for the ECF and PV expansion have not been clearly defined.