The responses of cell types in peri-implant tissues to cobalt-chrome and titanium were studied in vitro. Cylinders were made from both a cobalt-chrome alloy and commercially pure titanium (length 6 mm, diameter 7.9 mm). Plastic tubes were placed over the cylinders to create cell culture wells, in which human epithelial cells or mouse fibroblasts were cultivated. Cell viability was studied using the Alamar Blue method. The surface structure of two samples of each material was analyzed with optical interferometry. The morphology of cells grown on cylinders of each material was studied with scanning electronic microscopy. Epithelial cells and fibroblasts in the titanium group were more viable than those in the cobalt-chrome group (p = 0.001 and p = 0.000, respectively). The titanium surfaces had a greater height deviation (S(a), p = 0.027) but were less dense (S(ds), p = 0.044) than the cobalt-chrome group. The scanning electronic microscopy revealed no major deviations from normal cell morphology. Within the limitations of the present study, the findings indicate that epithelial cells as well as fibroblasts have a stronger negative response to cobalt-chrome alloy than to titanium. We suggest that these differences can be explained only bythe material per se and not by the minor differences in surface structure. Further and clinical studies are needed to confirm the significance of these findings.