We present the first analysis of the sites of expression of DNA topoisomerase II alpha and II beta mRNAs in human foetal tissues by in situ hybridisation, using 35S-radiolabelled probes. This revealed differential localisation of topoisomerase II alpha and II beta mRNAs in a range of foetal organs, including foetal kidney (developing structures within the neogenic zone), brain (cortical layers), small intestine (crypt epithelium and muscle), liver (hepatocytes), lung (smooth muscle, and epithelium in the lining of primitive lung buds) and placenta (trophoblastic epithelium). The intensity of expression of topoisomerase II alpha mRNA appeared higher than that of topoisomerase II beta, although topoisomerase II beta mRNA was expressed in a broader range of cell types. The distinct patterns of expression of topoisomerase II alpha and beta mRNAs indicate differential regulation of these genes, suggesting that the two isoforms may play important but different roles in foetal development, with topoisomerase II alpha being expressed most strongly in zones of proliferation.