A randomized controlled clinical trial comparing six combined oral contraceptives with 50 micrograms or less of ethinyl estradiol was undertaken in 10 WHO Collaborating Centres for Clinical Research in Human Reproduction. A total of 2430 women entered the trial and were observed for 28,077 woman-cycles. All low-dose combined oral contraceptives demonstrated equivalent efficiency with one-year pregnancy rates of one to six percent. However, discontinuation rates for medical reasons differed significantly between the treatment groups, with the preparation containing 20 micrograms ethinyl estradiol and that containing 400 micrograms norethisterone acetate being associated with higher discontinuation rates due to bleeding disturbances. Even among the preparations which did not differ in discontinuation rates, the reasons for discontinuation did differ. Women receiving norethisterone preparations tended to discontinue because of bleeding disturbances while those receiving the levonorgestrel-containing preparations tended to discontinue because of complaints of nausea and vomiting.