The concentration of serum cotinine (the major metabolite of nicotine) was measured in sera from 4211 women at between 15 and 21 weeks gestation to determine whether a serum cotinine level was a better predictor of low birthweight than the self-reported number of cigarettes smoked per day. Both cotinine levels and smoking history were significantly associated with reduced birthweight, but cotinine correlated significantly better. Smokers of greater than or equal to 25 cigarettes per day, representing the 2.7% of women with the greatest cigarette consumption, had infants 289 g lighter than the 68% of women who were nonsmokers. Women with serum cotinine levels in the top 2.7% (greater than or equal to 284 ng/ml) had infants 441 g lighter than the 68% of women with the lowest cotinine levels (less than or equal to 24 ng/ml). Our results strengthen the evidence linking smoking with low birthweight and also demonstrate that cotinine can be satisfactorily used to assess and monitor cigarette smoking in pregnancy.