To determine the effects of sex and menstrual cycle phase on CYP3A activity and to characterize the intraindividual variability of CYP3A, 24 Caucasian adults were given a single dose of omeprazole every 14th day for 3 months (men) or during the mid-follicular and mid-luteal phases over 3 full menstrual cycles (women). The 2-hour plasma metabolic ratio (MR) (omeprazole/omeprazole sulphone) was used as a measure of CYP3A activity. Overall mean MRs for men (2.4 +/- 1.2) and women (2.3 +/- 0.93) were not significantly different. In women, no difference in mean omeprazole MR was observed between the mid-follicular phase (2.2 +/- 0.85) and mid-luteal phase (2.4 +/- 1.0). When all data in the mid-luteal phase were stratified into 3 groups based on the progesterone concentrations (>50 nM [A], 20-50 nM [B], and <20 nM [C]), the MR of group A was significantly lower than that of B and C. The MRs of women during the mid-luteal phase were weakly correlated with progesterone concentrations (r = -0.35; P = .03). Individual coefficients of variation (CV%) in MR ranged from 8.7% to 60.2%, with a median 30.0%. No sex or menstrual cycle differences in CYP3A activity as measured by the probe drug omeprazole were seen. Higher CYP3A activity in women may be associated with higher endogenous progesterone concentrations.