The restriction site mutation assay (RSM) can be used to measure base changes which occur in the DNA coding for bacterial restriction enzymes, The aim of this study was to investigate whether DNA, of sufficient quantity, and quality for analysis by RSM, could be extracted from cells collected from precancerous lesions using a cytological smear technique, Six smears were collected from each of five lesions of leukoplakia displaying a variety of clinical appearances. Three methods for the extraction of DNA were compared. The commercial extraction method was shown to be most convenient and reproducible, routinely providing 1-5 mug of DNA per sample. Cell populations collected by a Cytological smear technique can provide DNA of sufficient quantity and quality for analysis of RSM. (C) 2001 Wiley-Liss, Inc.