A single application of APF to sound enamel before exposure to an artifical caries system in vitro had no effect on subsequent lesion formation. However, when initial lesions were treated with APF (1.23%F) and re-exposed to the artificial caries system histological changes were produced indicative of remineralization within the lesion. This suggests that topically applied fluoride may exert its maximal effect on initial lesions rather than on sound enamel.