During oral treatment with 3 mg micronized 17 beta-estradiol and 0.150 mg desogestrel for 21 days followed by 0.030 mg (A) desogestrel (15 women) or placebo (B) (14 women) for 7 days, ovarian function, bleeding pattern and estradiol levels were evaluated. The study was performed in a group-comparative, double-blind fashion. During a pre-treatment control cycle, using ultrasound scan, follicular diameter was measured on cycle days 10-16 and endometrial thickness on one of cycle days 22-26. Estradiol was measured at the time of ultrasound scan and progesterone three times in the luteal phase. During three treatment cycles, follicular diameter and endometrial thickness were monitored three times weekly and at the same time, estradiol and progesterone were measured. Treatment resulted in anovulation in all women. Maximum and mean estradiol levels were approximately 900 pmol/l and 550 pmol/l during treatment, respectively, and approximately 200 pmol/l during the estradiol-free weeks in both groups. Ten women showed ovarian activity (follicle size > or = 15 mm) during treatment, seven in group A and three in group B. Endometrial thickness decreased approximately 3 mm during treatment in both groups. The incidence of breakthrough bleeding and spotting was higher in group A when compared to group B. The study indicates that the combination of 3.0 mg micronized estradiol and 0.150 mg desogestrel is an effective and safe contraceptive, offering an acceptable cycle control. The addition of a low dose of desogestrel during the pill-free period did not further suppress ovarian activity nor improve the bleeding pattern. The results of this study should be interpreted with great care, since the number of women studied is relatively small. :Although natural estrogens have the potential to eliminate the adverse hemostatic effects associated with high-dose synthetic estrogen, such regimens have been associated with a high incidence of irregular bleeding and difficulties maintaining sufficient circulating estradiol levels for at least 24 hours. To identify strategies for improving this bleeding pattern, 36 women were randomly allocated to receive either 3 mg of desogestrel during the 7-day pill-free interval (group A) or a placebo (group B); for the 21 preceding days, women in both groups were treated with 3 mg of micronized 17 beta-estradiol and 0.150 mg of desogestrel. Ovulation was inhibited in all women in all three treatment cycles monitored. Mean estradiol levels were 550 pmol/l during treatment and 200 pmol/l during the estradiol-free period in both groups. Seven women from group A and three from group B showed ovarian activity (follicle size equal to or greater than 15 mm). Two women, both from group A, developed asymptomatic ovarian cysts with a diameter of 30 mm or greater. Women in both groups showed a decrease in endometrial thickness of approximately 3 mm. Breakthrough bleeding occurred in 30 (34.5%) of the 87 cycles available for analysis; the addition of desogestrel in the pill-free period had no effect on the bleeding pattern. Although these findings suggest that the addition of desogestrel to the pill-free interval neither improves the bleeding pattern nor further suppresses ovarian activity, the number of subjects was too small to permit final conclusions.