Previous studies have reported both direct and indirect evidence correlating the probability of conception by IVF-embryo transfer with follicular metabolism of glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 betaHSD). To resolve disputes regarding the predictive value of measures of cortisol-cortisone interconversion, this study has focused on compounds present in follicular fluid that can regulate enzyme activities within the ovary. Follicular fluid contains both hydrophilic compounds that can stimulate and hydrophobic components that can inhibit the oxidation of cortisol to cortisone by 11 betaHSD. These latest data indicate that: (i) cortisol:cortisone ratios in follicular fluid increase in proportion to the follicular content of the hydrophobic inhibitors of 11 betaHSD (r2 = 0.076; P < 0.01); (ii) the developmental potential of the oocyte and embryo, in terms of the probability of conception subsequent to embryo transfer, is positively correlated with follicular cortisol:cortisone ratios (12.9 +/- 0.3 in conception cycles versus 8.5 +/- 0.2 in non-conception cycles, P < 0.0001; odds ratio = 3364.48, P < 0.001); (iii) conception by IVF-embryo transfer is associated with increased concentrations of the ovarian inhibitors of 11 betaHSD (odds ratio = 4.54, P < 0.01) but with decreased concentrations of the ovarian stimuli of 11 betaHSD (odds ratio = 0.18, P < 0.001).