All-trans-retinoic acid (RA) affects cell growth and regulates gene expression. We examined the expression of topoisomerase 11 gene in Hep3B cells treated with RA. At low RA concentration which did not significantly affect the growth rate of Hep3B cells, RA inhibited the synthesis of topoisomerase II mRNA as revealed by Northern analysis and nuclear run-on analysis. These results indicated that the repression of topoisomerase II gene expression could be directly induced by RA rather than was a secondary event which occurred after cell growth was inhibited by RA. An unexpected finding is that after up to 72 h continuous exposure to RA, the topoisomerase II protein concentration remained unchanged.