During a cross-over study with young female volunteers, the effects of a combination of 30 µg ethinylestradiol (EE) and 150 µg desogestrel (DG) or 3-keto-desogestrel (KDG) upon lipid metabolism were investigated on day 3 of the first cycle (day 3/1) and on day 21 of the third cycle of treatment (day 21/III). As compared to the control cycle, total cholesterol (CH), low-density lipoprotein CH (LDL-CH), and the apolipoproteins A-II and B were reduced already on day 3/1, the effects being more pronounced with the DG-containing formulation. On day 21/III of treatment with EE/DG, the levels of total CH, LDL-CH and apolipoprotein B did not differ from controls, while apolipoprotein A-II was significantly increased. The effects of EE/KDG were similar, except that on LDL-CH which was still reduced on day 21/III. The serum concentrations of total triglycerides (TG), very low-density lipoprotein CH (VLDL-CH), VLDL-TG, LD-TG, high-density lipoprotein CH (HDL-CH), HDL-TG, and apolipoprotein A-I were not significantly affected on day 3/1, but elevated on day 21/III. As during treatment with EE/KDG the peak level of KDG was higher than with EE/DG, the results indicate a more pronounced antagonistic effect of EE/KDG on some EE-induced changes on lipoproteins during the first days of intake. These short-term changes possibly reflect a rapid enhancement of hepatic uptake of remnants and LDL by EE. During long-term treatment, the other effects of EE, e.g. the stimulation of hepatic synthesis of TG, VLDL, and HDL and the inhibition of hepatic lipoprotein lipase, become apparent.