Possible changes in protein metabolism during the menstrual cycle were examined in eight healthy women who received an intravenous infusion of L-[1-13C]leucine on time during the follicular phase of the menstrual cycle and one time during the luteal phase. Enrichment of plasma [13C]ketoisocaproate and expired 13CO2 were measured to determine leucine flux and oxidation. Continuous respiratory gas exchange measurements were made for the determination of CO2 production, O2 uptake, and energy expenditure. The day of the tests, plasma thyroid hormone concentrations were measured as well as plasma and urinary cortisol. Leucine flux was higher during the luteal than during the follicular phase (2.25 +/- 0.39 vs 2.01 +/- 0.42 mumol.kg-1.min-1; P < 0.01), and leucine oxidation was also increased during the luteal phase [0.52 +/- 0.14 vs. 0.44 +/- 0.05 mumol.kg-1.min-1 (P < 0.05) for luteal and follicular phases, respectively]. Resting energy expenditure was increased during the luteal phase compared with the follicular phase (218 +/- 22 and 199 +/- 12 kJ/h, respectively). Plasma free triiodothyronine (T3) and the ratio triiodothyronine/reverse triiodothyronine (T3/rT3) were both significantly higher during the luteal phase [7.7 +/- 0.6 vs. 7.1 +/- 0.8 and 4.65 +/- 0.80 vs. 3.93 +/- 0.70 for T3 and T3/rT3, respectively (P < 0.05 for both comparisons)]. This study shows small changes in protein metabolism during the menstrual cycle in women, with an increase in oxidative leucine metabolism during the luteal phase. The concomitant increase observed in circulating free T3 raises the possibility that fluctuations in protein metabolism and thyroid hormones throughout the menstrual cycle are causally related.