Objective: To examine the effect of clomiphene citrate ( CC) on the ovarian, endometrial, and cervical histologies in a rat model. Methods: The rats (n = 40) were randomly assigned to 4 treatment groups: CC 50 ( repetitive doses of 0.2 mg CC); CC 100 ( repetitive doses of 0.4 mg CC); CC 200 ( repetitive doses of 0.8 mg CC), and control ( repetitive doses of normal saline). Each study group received its CC dose intraperitoneally in 2 ml saline for 5 days and the controls received 2 ml saline only. Each treatment cycle was repeated six times. Six months later the rats were euthanized. Their ovaries, uterine horns, and cervices were removed and examined for histologic changes. Results: We found no significant difference in the number of follicles and corpora lutea of the study groups ( p >0.05). The numbers of granulosa, theca, and luteal cells of the CC 100 and CC 200 groups were significantly higher than those of the CC 50 group and controls ( p < 0.05). There was no important finding related to pre-malign and malign changes in ovarian, endometrial and cervical samples of the control and CC 50 groups. Focal atypia and atypical mitoses were noted in 2 cases of granulosa cells in the CC 100 and CC 200 groups. Conclusion: We did not find an association between the use of CC and ovarian, endometrial, and cervical neoplasms; nevertheless, we noticed an increase in granulosa, theca and luteal cells with high doses of CC, which may be a risk factor for granulosa, theca, and luteal cell tumors. Copyright (C) 2005 S. Karger AG, Basel.