Guanidine hydrochloride (GHCl) is frequently used for the isolation of RNA from eukaryotic cells. However, it appears that its use for the rapid isolation of chromosomal DNA has been little appreciated. Intact and readily digestible DNA was prepared from a range of murine tissues and cell lines which had been dispersed in GHCl and ethanol precipitated, and then rinsed in 70% ethanol and resuspended in 10 mM Tris-HCl, 1 mM EDTA, pH 7.5. This simple technique is ideally suited to the preparation of DNA from large numbers of tissue samples.