Abstract Objectives. This in-situ study aimed to investigate the potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) crème and fluoride mouth rinse to re-harden erosively softened enamel and to evaluate the influence of an intra-oral or extra-oral application. Methods. Ten volunteers performed five experimental series. Per series, four bovine enamel samples were extra-orally softened by immersion in Sprite light (2 min) and subsequently worn intra-orally for 5 min in intra-oral appliances. Thereafter, samples were treated (3 min) with either 250 ppm AmF/SnF(2) solution (Meridol) (series 1 and 3) or CPP-ACP crème (Tooth Mousse) (series 2 and 4). Application of the substances was performed extra-orally (series 1 and 2) or intra-orally (series 3 and 4). Untreated specimens served as control (series 5). The appliances were worn for 4 h afterwards. Knoop microhardness (KHN) measurement was performed at baseline, after softening and after completing of the respective run. Data were statistically analyzed by ANOVA and Bonferroni/Dunn post-hoc test. Results. No significant difference in baseline microhardness was observed, while immersion in Sprite light reduced the microhardness significantly. Significant re-hardening after intra-oral exposure occurred in all series, but baseline microhardness was not achieved. Microhardness in series 2 was significantly higher than that in series 1 and 5. No significant differences in KHN were detected between series 3, 4 and 5. The re-hardening ΔKHN (final microhardness - microhardness after erosion) was not significant different in all five series. Conclusion. Intra-oral application of CPP-ACP crème or fluoride solution provides no benefit regarding re-hardening of erosively softened enamel.