The present study was carried out to examine the effect of application of a fluoride varnish (Duraphat) on experimentally produced caries in vivo. After a 4-wk period of cariogenic challenge on homologous pairs of premolars, Duraphat was applied on one of the teeth while the other was extracted and saved as a control. The Duraphat treated teeth remained in a cariogenic environment for a new period of 2 wk prior to extraction. All the control teeth displayed the classical characteristics of active incipient subsurface carious lesions. The Duraphat treated lesions showed an increase in surface porosity relative to their controls while the subsurface porosity was dramatically reduced. When examined in the SEM, the corresponding surface appeared smooth with a leveling out of the original surface irregularities. High power microscopy disclosed, however, a distinct network of intercrystalline spaces. Application of Duraphat prior to reestablishment of cariogenic challenge apparently gives rise to a marked redistribution of minerals in active initial carious lesions.