Metabolic and hemostatic effects of 2 low dose oral contraceptives (OCs), a triphasic (ethinylestradiol + (-)-norgestrel) and a monophasic (ethinylestradiol + desogestrel) preparation, were compared in a cross-over trial in fertile women over 35 years of age. Both combinations moderately affected plasma lipids, with 17-24% increases of total triglyceridemia. Triglycerides accumulate in low density lipoproteins, thus suggesting the possible formation of an atherogenic lipoprotein particle. Only the monophasic preparation increased high density lipoprotein (HDL)-cholesterol levels significantly, with a rise in HDL3 mass and cholesterol. OC treatment led to slight changes in HDL2 and HDL3 structure, with a rise of the cholesteryl ester and triglyceride contents, indicative of a stimulated cholesterol esterification and reverse transport. Changes in the hemostatic indexes (fibrinogen, antithrombin III and protein C) were negligible. The new low dose OCs, even when prescribed to relatively older women, affect to a relatively small extent lipid/lipoprotein metabolism, with the exception of changes in the low density lipoprotein composition.