ABSTRACT Increases in serum triglycerides, cholesterol and pre-β- and β-lipoproteins have been considered as significant pathogenic factors regarding the possible thrombotic side-effect of treatment with oral contraceptives of the combined type containing synthetic oestrogen. With the purpose of investigating the influence of natural oestrogen (oestradiol-17β + oestriol/norethisterone acetate) versus synthetic oestrogen (ethinyloestradiol/norethisterone acetate) on serum lipids and lipoproteins in young women compared to independent and individual controls, as controlled double-blind investigation was performed in 33 women in a total material and 18 women in a selected group. The significant changes were as follows: quantitative increases in serum triglycerides (P < 0.001) and β-lipoproteins (P < 0.01) during treatment with synthetic oestrogen, while in contrast no such change was observed in subjects on natural oestrogen, which was found to decrease serum cholesterol (P < 0.05), phospholipids (P < 0.05) and α-lipoprotein (P < 0.05). Quantitative estimation of serum lipoproteins was found to be more valuable than the relative estimation by electrophoresis. It is concluded that oral contraceptives containing natural oestrogens induce less significant and, qualitatively, more benign changes in serum lipids and lipoproteins than preparations containing synthetic oestrogen do.