The effect of maternal nicotine exposure on lung growth in vivo in neonatal rats was investigated. Nicotine (0.25 and 1.0 mg/kg/day) administered subcutaneously to the pregnant animal from day 7 of gestation until weaning resulted in smaller neonatal lungs that were about 15% smaller on postnatal day 8. On day 21 no difference in lung mass occurs. Maternal nicotine exposure also causes enhanced lung cellular multiplication as judged by the calculated daily increase in DNA of 0.19 mg/g for control lung and 0.31 mg/g for experimental lung. Comparison of the protein/DNA ratio 5.75 +/- 0.22 of the control and the 3.59 +/- 0.21 of nicotine-exposed lungs showed that the cells of the latter was smaller. The lower lung mass was attributed to the smaller cell size. It is proposed that nicotine's marked inhibitory (42%) effect on glycolysis probably results in type I cell injury and consequently enhanced cell proliferation.