Lipids and lipoproteins were studied in controls and women using contraceptive vaginal rings (CVRs). The groups were comparable for race, age, parity, obesity indices, alcohol ingestion, smoking, diet and exercise. Fasting blood samples were obtained twice before CVR treatment, after 2 and 7 weeks of treatment and 1 week thereafter. The women using the CVR had a significant incremental reduction of cholesterol from baseline to treatment which was distributed among all the lipoprotein classes. The cholesterol/HDL-C ratio was significantly increased with treatment. All mena changes were within the reference range. The reduction in HDL and especially in the subclasses HDL 2a and HDL 2b were significant and outside the reference range. The LDL/HDL ratio increased significantly, while the LDL/HDL 2a+2b ratio increased significantly outside the reference range with treatment. Of the lipid and lipoprotein measurements that changed significantly with treatment, HDL-C, HDL, HDL 2a LDL/HDL and LDL/HDL 2a+2b changed significantly towards baseline in the 1-week-off treatment. The potential reduction in predicted coronary risk with the use of the CVR suggested by a reduction in cholesterol was counterbalanced by a reduction in HDL-C and increases in the cholesterol/HDL-C and LDL/HDL ratios. The potential clinical implications of these findings remain to be determined.