11 oophorectomized women (mean age 34.5 +/- 5.9) were given the 17-C-alkylated ethinyl estradiol (EE) 20 microgram/day and the non-alkylated estrogen, estradioil valerianate (E2V) 2 mg/day for 6 weeks in separate periods preceded by 6 weeks without hormonal replacement therapy. Blood samples were drawn before and after 6 weeks on each estrogen. Serum phospholipids, cholesterol and triglycerides were assessed. Preparative ultracentrifugation with the isolation of the very low density (VLDL; d < 1.006 g/ml); the low density (LDL; d = 1.006-1.063 g/ml) and the high density lipoprotein (HDL; d > 1.063 g/ml) fraction was carried out. In the three lipoprotein fractions, phospholipid, total cholesterol, free cholesterol and triglycerides were determined. An oral glucose tolerance test with concomitant plasma insulin determination was performed. In the present study EE caused an increase in serum total and LDL triglycerides while there was a reduction of triglycerides in serum as well as in VLDL and LDL when E2V ws administered. There was a positive correlation between plasma insulin values during oral glucose tolerance test and serum and VLDL triglycerides when E2V was administered. This finding supports earlier studies indicating that insulin (or rather the insulin-glucagon relationship) influences the hepatic triglyceride production rate. Both EE and E2V increased HDL cholesterol, but E2V did not induce a concomitant increase in serum triglycerides which would suggest a more physiological effect from the latter compound since fertile females have lower serum triglycerides and higher HDL cholesterol levels than males of corresponding age. The same differences are true in a comparison between fertile and post-menopausal women.