Objective: We assessed changes in creatinine clearance during the menstrual cycle of normally cycling women. Methods: We used a design that precisely identified the day of ovulation. Creatinine clearance was measured in 14 subjects on each of three days: cycle day 2 or 3, 1 or 2 days before the day of ovulation, and 6 or 7 days after ovulation. Results: Creatinine clearance was affected significantly by the menstrual cycle (P =.02), but the degree of this effect was modest. Mean (± standard error of mean) early follicular, preovulatory, and midluteal creatinine clearance values were 135 ± 4,131 ± 5, and 142 ± 5 mL/min, respectively, and only the difference between the preovulatory and midluteal values was significant. These changes in creatinine clearance were attributable largely to changes in creatinine excretion and not to changes in plasma creatinine concentrations. Conclusion: Despite the statistically significant luteal phase increase, creatinine clearance does not change in a clinically important manner during the normal menstrual cycle. Specifically, there is no substantial decrease in creatinine clearance around the time of ovulation.