Abstract To investigate the toxic effect of tobacco smoke on the fetus, we measured in cord blood the concentrations of -fetoprotein (AFP), the principal serum protein in early ontogenic development, and erythropoietin (EPO), as an index of chronic fetal hypoxia. A total of 103 consecutively enrolled term newborns of smoking mothers and 103 term infants of nonsmoking parents were studied. The meanSD AFP concentrations in the newborns of the mothers who smoked 150, 550, and 1050 cigarettes/day were 86.488.9, 96.391.9 and 118.7103.7ng/ml, respectively. The difference of all three groups from the control neonates (57.737.2) was significant. The EPO concentrations in the newborns of the mothers who smoked 150 (53.964.6mU/ml) and 550 (56.368.5) cigarettes/day were significantly greater than in the control neonates (29.516.1). In the newborns of the smoking mothers there was a significant positive correlation between AFP concentrations and number of cigarettes smoked per day, and a negative correlation between AFP and birth weight or length. There was no correlation between AFP and EPO concentrations, as well as between EPO and birth weight, length or number of cigarettes smoked per day. Conclusion The absence of a correlation between erythropoietin and birth weight or length and the negative correlations between -fetoprotein and these anthropometric parameters suggest that the intra-uterine growth retardation caused by maternal smoking is not due to tissue hypoxia, but that both growth retardation and elevated -fetoprotein result from the direct or indirect toxic effect of a factor(s) present in tobacco smoke.