Data were collected from 1275 pregnant Turkish women screened prospectively for chromosomal anomalies to determine whether first-trimester levels of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) and the thickness of nuchal translucency are affected by smoking and other covariables. Only normal singleton pregnancies were included. After weight correction, comparisons were made between smokers and nonsmokers. Mean values of PAPP-A and beta-hCG were reduced in women who smoked 5 or more cigarettes a day compared with nonsmokers. The median beta-hCG level decreased significantly as gravidity and parity increased; no effect was noted on PAPP-A. Median PAPP-A and beta-hCG levels tended to increase, but not significantly in women who had had 2 or more miscarriages. Smoking alters maternal levels of serum analytes, with the magnitude of the impact related to the number of cigarettes smoked per day. This effect can be detected in the first trimester of pregnancy.