The effects of oral contraceptives of varied estrogen/progestin composition on clinical measurements of hepatic, thyroid, and renal function and carbohydrate metabolism were examined in 1,355 women in the Lipid Research Clinics Program Prevalence Study. In general, bilirubin and alkaline phosphatase levels are lower with both oral contraceptives and postmenopausal estrogen use, suggesting an estrogen effect. The least bilirubin reduction is seen with a progestin dominant oral contraceptive. A significant decrement in aspartate aminotransferase is observed in users of one high estrogen dose oral contraceptive and in postmenopausal Premarin users, while aspartate aminotransferase is higher in postmenopausal users of higher dose ethinyl estradiol. Globulins are slightly higher in all hormone use categories, suggesting an estrogen effect on hepatic secretion of this protein class into the circulation. Fasting glucose concentrations are generally slightly lower even in the progestin dominant oral contraceptives, where glucose intolerance has been described. Thyroxine concentrations are generally elevated in all women using oral contraceptives. A relationship to estrogen dose is seen in women with thyroxine concentrations greater than the 99th percentile and in postmenopausal estrogen users. Creatinine concentration is greater with the use of Ovral, a progestin dominant oral contraceptive, and lower with two estrogen dominant oral contraceptives and Premarin, suggesting a competitive effect of estrogen and progestin. Among the clinical laboratory tests considered here, oral contraceptive effects seem to be largely estrogen mediated with a suggestion of competitive effect of estrogen versus progestin only on bilirubin and creatinine levels. These observations differ from lipoproteins where opposing hormonal effects are more clearly reflected in changing lipoprotein concentrations.