There is evidence for synergy between tobacco and alcohol in the etiology of oral cancer but the reason for such an effect is unclear. One possible explanation is that alcohol enhances the penetration of carcinogens through the oral lining. We measured the permeability in vitro of three regions of porcine oral mucosa to the tobacco associated carcinogen, nitrosonornicotine (NNN) alone and in the presence of 5% or 50% ethanol. 50% ethanol did not significantly alter the permeability of oral mucosa to NNN except for buccal mucosa, where it was reduced. However, there was a significant increase in the permeability of gingiva and floor of mouth mucosa (but not buccal mucosa) in the presence of 5% ethanol; this increase occurred after far shorter exposures for floor of mouth than for gingiva. These results accord well with studies showing that the floor of mouth is a "high risk area" for oral carcinoma and that there is an increased relative risk of oral cancer for heavy smokers and drinkers and, in particular, for those individuals who consume beverages with a low alcohol content.