The effects of maternal cigarette smoking on the transcriptome of human full-term placentas were investigated by a microarray analysis. QPCR was performed for a selected set of metabolizing genes. Differentially expressed genes were selected by fold change (+/-1.5-fold) and analysis of variance (P<0.05) between the control and smoker groups. The expression of 174 probe sets was affected significantly. Chronic cigarette smoking induced the expression of CYP1A1. A trend toward a decrease in the expression of several steroid hormone-metabolizing enzymes, including CYP19A1, was detected. The expression of phase II enzymes was not altered, and no enriched categories were observed among the regulated genes, except for aryl hydrocarbon receptor (AhR)-CYP1A1. The unaltered expression of phase II enzymes may result in an increase in the levels of active metabolites and elevated oxidative chemical stress in the placenta and the fetus. On the basis of our results, it seems that cigarette smoke acts as a hormone disrupter in the placenta.