The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.