To test whether adaptation to sorbitol could be observed in rat plaque, we made pH measurements of rat sulcal plaque in vivo, following topical application of 10% sorbitol solution. Rat pups were inoculated orally with S. mutans 6715 and fed diet MIT 305 (5% sucrose) for 16 days. Baseline sulcal plaque pH response of these rats to topical application of 10% sorbitol solution was measured. One group of 16 rats was then fed 20% sucrose in the diet, and a second group 20% sorbitol. After 13 days' feeding of the experimental diets (four days were used for accommodation to dose, and nine days at the 20% level for sorbitol), there was a significantly greater (p less than 0.01) drop in pH following topical application of 10% sorbitol in this group than in the sucrose-fed group. There was no difference in the pH response of the two groups to topical application of a 10% sucrose solution when tested six days later. The sulcal enamel caries score was significantly higher (p less than 0.001) in the sucrose group, but buccal enamel scores were similar in both groups. Adaptation in rat plaque took place, and could be measured in vivo as an increased drop in sulcal plaque pH following topical application of sorbitol. It is not clear whether this adaptation was primarily due to selection of sorbitol-fermenting micro-organisms, or, more likely, by induction of sorbitol-specific enzymes. Relative to the sucrose-containing diet, the sorbitol diet was hypocariogenic, even under experimental conditions.