Nicotine-delivering transdermal patches were applied to the back of timed-pregnant Sprague-Dawley rats. Pregnancy failure was 100% in animals exposed to 3.5 mg of nicotine per day during the entire pregnancy and 50% in animals exposed to the same amount during the first trimester. Application of 1.75 mg of nicotine per day resulted in a 50% pregnancy failure when exposure occurred during the entire pregnancy. In animals exposed for the first half of pregnancy to cigarette sidestream smoke, under conditions where plasma nicotine levels reached about 25% of those observed following exposure to 1.75 mg of nicotine per day, the average litter size was reduced by about 25%. It is concluded that continuous exposure to nicotine early during pregnancy may adversely affect pregnancy outcome in rats.