In an attempt to elucidate the effect of paramethasone acetate on the hormonal profile of the normal menstrual cycle, 5 clinically healthy women, aged 24-36 yr, with ovulatory cycles were studied during a control menstrual cycle and during treatment with paramethasone acetate (6 mg/day). The length of the untreated cycle was 29.2 +/- 2.3 days as compared to 29.0 +/- 3.1 days during the paramethasone-treated cycle. Peak plasma E-2 level was 188.2 +/- 42.1 pg/ml in the control cycle and 74.4 +/- 15.3 pg/ml during paramethasone treatment (P is less than 0.05). Peak plasma 17 OH-P was 4.0 +/- 0.4 ng/ml in the control cycle and 1.6 +/- 0.2 ng/ml during the paramethasone treated cycle (P is less than 0.005). No significant differences in plasma progesterone were observed during the luteal phase of both cycles. Minimal and scattered differences were observed in plasma FSH. However, plasma LH levels were lower in the paramethasone acetate than in the control cycle almost throughout the entire period of study. Furthermore, midcycle LH peak in the control cycle was 958 +/- 104 ng/ml as compared to 283 +/- 24 ng/ml during the paramethasone treatment (P is less than 0.005). Despite these differences, ovulation occurred during paramethasone treatment based upon the observed rise in BBT, the plasma progesterone levels above 6 ng/ml and the secretory changes in the endometrium. These results suggest that: 1) Paramethasone may block E-2 synthesis at the ovarian level and , 2) Ovulation may still occur even in the presence of E-2 and LH plasma concentrations lower than those occurring in the normal menstrual cycle.