Purpose: This study aimed to evaluate the hydrolytic behavior of different computer-aided design/computer-aided manufacturing (CAD/CAM) resin matrix ceramics (RMCs) in different food-simulating liquids (FSLs). Materials and methods: Five different CAD/CAM blocks, one from polymer-infiltrated ceramic networks (PICNs; Vita Enamic (EN)) and four from resin-based composites (RBCs; Lava Ultimate (UL), Cerasmart (CER), Brilliant Crios (BR), and Block HC (HC)) were selected. Forty specimens were prepared for each material, and they randomly distributed to each FSLs. The specimens were kept in a desiccator initially, then placed in 5 ml of liquid at 37±1°C for 30 days and weighed at various time intervals. Percentage mass change (Mg%), sorption (SP), percentage of liquid absorbed (SP%), solubility (SL), percentage solubility (SL%), and percentage of liquid absorbed by the polymer matrix (SPpm) water absorption of the specimens were evaluated. Significance was evaluated at p<0.05 levels. Results: Hydrolytic behavior of the materials showed statistical differences in terms of SP, SL, SP%, and SL% values depending on the liquid environment (p=0.001). The highest SP values were obtained from the HC material in saliva, and the lowest values were obtained from the BR in ethanol. The highest SL values were obtained from the CER and EN in heptane, and the lowest values were obtained from the HC in ethanol. However, all results detected in the study remained below the ISO threshold values. Conclusions: All materials tested exhibited clinically acceptable hydrolytic behavior over the time tested. Not only the material content but also many factors can affect the hydrolytic behavior.