The effect of exposure of mice for 5, 10 and 15 days to arecoline or/and caffeine on the frequency of sister-chromatid exchanges (SCEs) in bone-marrow cells was evaluated by using the fluorescence plus Giemsa technique. There was a significant increase in the frequency of SCEs after exposure to either arecoline or caffeine. When these two alkaloids were given in combination, the SCE frequency-enhancing effect was additive. The implications of coffee/tea drinking and betel chewing on oral cancer are discussed.