Maternal serum alpha-fetoprotein (AFP) levels between 15 and 19 weeks gestation were studied in relation to birthweight, gestational age, maternal weight, and daily cigarette consumption in 1739 pregnancies. All infants were born after the 28th week of gestation and all were without neural tube defects. Gestational age was estimated by early measurement of the fetal biparietal diameter. High maternal serum AFP, low maternal weight, and the number of cigarettes smoked per day were found to correlate with low birthweight, but not with gestational age. By testing the influence of the individual parameters on the subsequent birthweight, no significant correlation was found between the AFP levels and birthweight. Low birthweight was mainly a result of cigarette smoking and low maternal weight. Screening for AFP in the second trimester, therefore, seems to be of no value in predicting low birthweight when maternal weight is taken into consideration.