Biomaterials are frequently used in prosthetic devices designed to replace or support failing tissues or organs in patients. Material properties should elicit an appropriate response of surrounding tissues in terms of biocompatibility and bioacceptance, but all too often complications occur, such as development of atheroscerotic lesions at connecting sites between vascular prostheses and autologous bloodvessel or occurrence of (contracting) fibrous capsules. In all multi-stage processes leading to these complications functional alterations in many cell types may occur due to the presence of the biomaterial. In this study, a number of possible in vitro tests for evaluation of cell function are discussed.Cell proliferation plays a prominent role in many tissue responses. Therefore BrdU incorporation is often used in EIA set-ups. In this study we additionally determined DNA content off human skin fibroblast populations adhered to silicone surfaces with different textural surfaces. Harvested cells were lysed, permeabilized and treated with the intercalating blue-excited dye propidium iodine (PI) plus RNAse. PI binds to DNA and double-stranded RNA. The resulting nuclei suspension was analysed with a flow cytometer. Resulting linear red fluorescence histograms of 20,000 cells were analysed with MultiCycle software with fitting procedures. Besides differences in the kinetics of G0/G1, S and G2/M phase on the different surfaces at different times, many subtle differences in DNA histograms attributable to the different surface geometrys and incubation times were detected. Side and forward scatter data together with information on the number of cells analysed per second provided additional data on the fibroblast-silicone interaction.Functional tests also include determination of viability and vitality, e.g. through MTT. They are based on the presence of enzymatic activity and membrane integrity in vital cells. Some current methods for determination of apoptosis, i.e. induced by materials, can be classified in the same group. Morphological data often provide a first estimate of cell performance on different materials. On a series of amalgams and amalgam alloys absence of cytotoxicity in indirect contact tests (extraction tests), as determined with BrdU-incorporation and MTT tests, coincided with a healthy human fibroblast morphology, whereas the cytotoxic dental materials gave rise to round-up shapes and decreased adherence. Despite absence of cytotoxicity differences in morphology were observed ranging from monolayer structures through colony-like growth to well-spread single cells. Functional correlates cannot always be clearly defined.In summary, a panel of testing methods for specific cell functions can be developed for in vitro evaluation of cell-material interactions. The results of these methods should be evaluated with the in vivo situation in mind. Furthermore, results often are ambiguous due to the complex biological system involved in cell responses. Increasing knowledge on signal transduction mechanisms inside and between cells will lead to development of additional methods. Despite these advanced methods for testing of cell function morphological evaluation will remain a key point.