The aim of the present study was to evaluate the effect of different irradiation doses after desensitizer application on the onset of initial demineralization of human dentin in situ. The root surfaces of 45 freshly extracted caries-free human molars were cleaned, thereby removing the cementum. From each tooth two root dentin specimens were prepared. The specimens were distributed among the following experimental groups: 0, 0.5, 1, 2 and 5Gy. The irradiation dose was fractionally applied (0.5Gy/day). One dentin specimen of each group was inserted into both buccal aspects of nine intraoral mandibular appliances. On one side the specimens were additionally coated with the desensitizer Hyposen (H). On the other side, the specimens were left untreated (C). The appliances were worn by nine persons for five weeks day and night. During meals, the appliance was stored in 10% sucrose solution. After the in situ period, slabs (150microm) were ground and studied using a polarized light microscope. Concerning radiation dose, significant differences were observed between the control and 5Gy group (p<0.05, Tukey s test). Pairwise comparison showed that lesion depths in groups treated with Hyposen were significantly decreased. Within the limitations of this study it can be concluded that higher radiation doses seem to increase the caries susceptibility of dentin. The additional application of a desensitizer hampers the demineralization and might have a caries-protective effect on exposed irradiated root surfaces.