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Flow cytometric analysis of cell cycle fractions and DNA ploidy was performed on 39 biopsy specimens of oral leukoplakia. The aneuploidy rate of these leukoplakias was 9/39 (23.1%) and the mean DNA index of the aneuploid lesions was 1.34. The aneuploidy rate was significantly higher in severely dysplastic lesions (8/17) than in mildly dysplastic (1/15, P<0.02) and nondysplastic (0/7, P<0.05) lesions. No significant differences in the percentages of each cell cycle fraction were seen between the diploid and the aneuploid leukoplakias. However, the S-phase fraction of the severely dysplastic lesions (23.0%) among the diploid leukoplakias was higher than those of the midly dysplastic (12.4%) and nondysplastic (15.5%) lesions, and the difference between the severely dysplastic and the mildly dysplastic lesions was statistically significant (P<0.001). These results suggest that flow cytometric analysis of cell cycle fractions and DNA ploidy might offer additional information for assessing the malignant potential of oral leukoplakias.