Objectives: To assess which clinical parameters influence human oocyte zona pellucida (ZP) thickness. Patients: Sixty-five couples undergoing 75 IVF-ET cycles. Main Outcome Measure: Zona pellucida thickness of 827 oocytes measured 16 to 20 hours after in vitro insemination under inverted light microscope. Results: Zona pellucida thickness was 18.9 +/- 3.8 mu m (mean +/- SD) for unfertilized, 16.4 +/- 3.1 mu m for fertilized, and 15.1 +/- 2.4 mu m for polyspermic oocytes (significantly different). Among our patients, a few underwent two for even three) IVF-ET cycles, and the mean ZP thickness was, in most cases, not significantly different from one cycle to the other(s). Regression analyses were calculated between ZP thickness anti available clinical parameters, i.e., the age of the women, the duration of stimulation, the cumulus maturity, the number of retrieved oocytes, the number of hMG doses, the maximum E(2) level, and the follicular volume. A significant linear decreasing relationship exists between the mean ZP thickness of each patient and the maximum E(2) level and an increasing one with the hMG dose. Relationships with the other parameters appeared to be nonsignificant. Conclusion: The ZP thickness is basically an individual feature that influences the fertilization rate, Nevertheless, it may be influenced slightly by the hormonal treatment during stimulation.