There is some evidence that plaque can adapt to regular exposure to some bulk sweeteners, leading to increased metabolism and acidogenic potential of the sweetener. This potential for adaptation varies between non-sugar sweeteners and has important implications for manufacturers of food, confectionery and medicines used long-term. Maltitol (99% purity crystalline D-maltitol) is a relatively newly approved non-sugar sweetener and appears to have potentially good dental properties. To compare plaque adaptation to pure sucrose, sorbitol, xylitol or maltitol and the effect of their prolonged use on acid production by plaque from sucrose, in vivo. Two series of plaque pH experiments were carried out. Each experiment involved a 14 day adaptive period when four 5 g lozenges of the sweetener were taken between meals each day. Each experiment was separated by a 14 day wash-out period. Acid production was quantified as: (a) minimum pH; and (b) cH area (difference between plaque pH curve and resting value, expressed as cH units). Thirteen adults, of mean age 41 years completed the study. When adaptation of dental plaque to the metabolism of sweeteners was compared, there was a statistically significant difference (p = 0.033) between xylitol and sorbitol, and between xylitol and sucrose but not between xylitol and maltitol. When the effect of prolonged use of sweeteners on acid production after sucrose rinsing was compared, there were no statistically significant differences between the sweeteners. Dental plaque does not adapt to metabolise xylitol or maltitol following prolonged exposure over 14 days.