The effects of tobacco and oral contraceptive (OC) use (Ovral) on the pharmacokinetics of levonorgestrel (0.25 mg) and ethinyl estradiol (50 μg) were examined. Young women (n = 27) were grouped as follows: I: non‐OC users/nonsmokers; II: OC users/nonsmokers; III: non‐OC users/smokers; and IV: OC users/smokers. The apparent clearance of levonorgestrel in group I was 80.9 ± 15.6 ml/hr/kg and the half‐life was 19.3 hours. A significant decrease in levonorgestrel clearance was seen in the chronic OC users (groups II and IV). The apparent oral clearance of ethinyl estradiol was 1002 ± 398 ml/hr/kg in group I and the half‐life averaged7.7hours. Groups II and III showed decreased (not significant) clearances of ethinyl estradiol. Tobacco use had no effect on steroid pharmacokinetics in the non‐OC users. Although chronic OC use did not affect ethinyl estradiol clearance, a joint effect of tobacco/OC use on enhancing clearance of ethinyl estradiol appeared to occur. A linear relationship was found between 24‐hour trough serum concentrations and AUC values of both steroids that may facilitate population monitoring studies of OC exposure.Clinical Pharmacology and Therapeutics(1988)43,23–31; doi:10