Several recent studies have established maternal smoking as a significant risk factor for sudden infant death syndrome (SIDS). To test our hypothesis that nicotine, a component of cigarette smoke, may exert an injurious effect on the fetal brain stem, we administered nicotine in drinking water to Sprague-Dawley rats prior to and throughout the first 20 days of gestation. The nicotine dose and schedule of consumption in this experiment paralleled that of human usage. Fetuses from nicotine-treated mothers had significantly more dead cells in a standard section of the medulla than controls, but little difference was observed in the postnatal respiratory responses of treated and control animals to the inhalation of various gas mixtures. The birth weights of nicotine-exposed fetuses were significantly less than those of controls. Although the degree of fetal brain stem injury produced by nicotine in this experiment is small, it is our concern that maternal smoking might cause a more severe lesion in the human fetus and thereby increase the risk of SIDS by contributing to aberrant postnatal respiratory responses to noxious stimuli.