The effects of various doses, duration and frequency of cimetidine treatment on vaginal cycle, ovulation, ovarian histology and follicular kinetics were investigated. In addition,studies were performed to assess the reversibility in ovarian functions following withdrawal of cimetidine treatment.A statistically significant (P<0.05) decline in ovarian and uterine weights, but not in body and adrenal weights, were observed in females treated with cimetidine four times daily for long-term as compared with the controls. Ovarian and uterine weights recovered to pretreatment levels following withdrawal of the treatment. Cimetidine treatment caused irregularities in the reproductive cyclicity of mice.Cimetidine treatment causes adverse effect on ovarian function depending on the time,duration and frequency of treatment. Treatment for only one day at proestrus induced significant (P <0.05) decline in ovulatory efficiency. However, administration of cimetidine, four times daily, for either 6 or 14 days caused ovarian dysfunction. The treatment depressed the number of healthy preantral and antral follicles as well as number of healthy corpus luteum (CL) in the ovary. Absence of healthy CL, presence of several atretic late antral follicles and reproductive acyclicity provide evidence for the failure of ovulation in mice treated with cimetidine four times per day for 14 days. Moreover, when cimetidine was administered twice daily, the ovaries also showed newly formed CL. The results, thus,suggest that the effects of cimetidine on ovulation are dependent on dose, duration and frequency of treatment. Blockage of ovulation in long-term cimetidine treated mice could be due to its influence on follicular atresia. Ovulation had occurred in these females after withdrawal of cimetidine treatment The effects of various doses, duration and frequency of cimetidine treatment on vaginal cycle, ovulation, ovarian histology and follicular kinetics were investigated. In addition, studies were performed to assess the reversibility in ovarian functions following withdrawal of cimetidine treatment. <0.05) decline in ovarian and uterine weights, but not in body and adrenal weights, were observed in females treated with cimetidine four times daily for long-term as compared with the controls. Ovarian and uterine weights recovered to pretreatment levels following withdrawal of the Cimetidine treatment caused adverse effects on ovarian function according to the time, duration and frequency of treatment. Treatment for only one day at proestrus induced significant (P <0.05) decline in ovulatory efficiency However, administration of cimetidine, four times daily, for either 6 or 14 days caused ovarian dysfunction. The treatment depressed the number of healthy preantral and antral follicles as well as number of healthy corpus luteum (CL) in the ovary. Absence of healthy CL, presence of several atretic late antral follicles and reproductive acyclicity provide evidence for the failure of ovulation in mice treated with cimetidine four times per day for 14 days. Moreover, when cimetidine was administered twice daily, the ovaries also showed newly formed CL. The results, thus, suggest that the effects of cimetidine on ovulation are dependent on dose, duration and frequency of treatment. Blockage of ovulation in long-term cimetidine treated mice could be due to its influence on follicular atresia. Ovulation occurred occurred in these females after withdrawal of cimetidine treatment