Purpose: The aim of the presented study was to investigate cellular reactions to different, commercially available collagen membranes and give recommendations for use as well as application instructions. Materials und Methods: The collagen membranes Gesitlich BioGide® (BG), Gesitlich Mucograft® (MG), BEGO Collagen Membran® (BEG), Mucoderm® (MD) und Collprotect® (CP) have been investigated histologically and histomorphometrically. In a standardised study, protocol membranes have been implanted subcutaneously in Wistar rats/CD-1 mice for up to 60 days and analysed with a focus on tissue reaction and a potential inflammatory response. Results: The histological analysis showed distinct differences regarding the cellular reactions to the different collagen membranes. BG and MG induced mononuclear cells (e.g. macrophages) as a sign of high biocompatibility, material integration and lack of a foreign-body-reaction. In contrast, the cellular reaction to BEG, MD and CP consisted of multinucleated giant cells, which arise from macrophages and migrate in the implantation bed. BG, MG and BEG showed complete volume stability and integrity. MG, a three-dimensional bilayered collagen matrix, presented cell ingrowth on the spongy surface, while the compact surface served as a stable barrier. MD showed continuous ingrowth of connective tissue along preformed landmarks from fat cell lacunae and vessel luminae. CP presented ingrowth of connective tissue and a reduction in membrane thickness to 75% of the original thickness. Conclusion: For the clinical application of collagen membranes, a detailed knowledge of the cellular reactions induced in the implantation bed is of considerable importance. Cellular reactions, as well as volume stability and membrane permeability, have a distinct influence on clinical success and have been analysed systematically in the presented study. Clinical relevance: Collagen-based membranes serve in periodontology and implantology as versatile barriers which separate different tissues and cells during the healing process. In addition to volume stability and membrane permeability, cellular reactions are, depending on the indication of the membranes, important material characteristics to achieve long-term stability and clinical success. Keywords: collagen membrane, GTR, GBR, Bio-Gide, Mucograft