BACKGROUND With the recent focus of researches on the development of non-invasive treatment modalities, the non-invasive treatment of early carious lesions by remineralization would bring a major advance in the clinical management of these dental defects. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is considered to be effective in tooth remineralization. OBJECTIVE The aim of this in-vitro study was to compare the effects of whey and CPP-ACP in increasing the enamel microhardness. METHODS Microhardness of 30 sound human permanent premolars was measured before and after 8-minute immersion of samples in Coca-Cola. The teeth were then randomly divided into 3 groups and were immersed in artificial saliva, whey, and tooth mousse for 10 minutes. The changes of microhardness within each group and among the groups were recorded and analyzed using paired t-test. RESULTS The microhardness increased in each group and between the groups; this increase was statistically significant (p= 0.009). CONCLUSIONS The effect of whey on increasing the enamel microhardness was more than that of tooth mousse.