Morphological changes occur in breast ductal epithelium during menstrual cycle. Electrical contact with ductal epithelium was established using a nipple electrode in 51 pre-menopausal women scheduled for breast biopsy. Epithelial impedance spectroscopy (EIS) measurements were obtained over a frequency range of 0.1 Hz-60 kHz. Seven of the 51 patients tested had ductal hyperplasia and demonstrated a high transepithelial ductal resistance (Re), 225 59 k Omega, that did not appear to vary during menstrual cycle. However, significant differences were observed in patients with non-proliferative disease tested in week 1 and 4 of cycle (Wk 1, 4), (n=23) compared to those tested in week 2 and 3 (Wk 2, 3), (n=21). Re of the ducts were higher in Wk 2, 3 with values of 281 +/- 59 Omega compared with an Re of 114 19 k Omega in patients tested in Wk 1, 4 (p < 0.05). The capacitance of the ductal system appeared non-significantly higher in Wk 1, 4 with a value of 8.40 +/- 7.70 mu F, compared with 0.28 +/- 0.03 mu F in patients tested in Wk 2, 3, (p = 0.097). This study demonstrates that menstrual cycle affects the electrical signature of the ductal epithelium in patients with benign breast disease, and can be measured non-invasively. Atrophic breast epithelium, and apoptotic epithelium in weeks 1 and 4 of cycle, respectively, appears to have a lower Re than differentiated, multilayer epithelium of mid-cycle. EIS may be of use in identifying proliferative changes in the ductal epithelium of women during menstrual cycle.