Bio-Micro-Electro-Mechanical Systems (BioMEMS) are a new tool in life sciences, supporting cell biology research by providing reproducible and miniaturized experimental platforms. In order to cultivate cells in such systems, appropriate microenvironmental conditions are required. Due to the multitude and variety of microbioreactors and cultivated cell types available, standardized cell handling methods and comprehensive biocompatibility data are sparse. The bioreactor developed at Ilmenau University of Technology features BioMEMS consisting of silicon, glass, and polymers, supplied by peripheral components. To verify the system's suitability for cell cultivation, it was necessary to prove whether materials and surfaces are biocompatible. Custom-tailored biocompatibility test procedures along with adequate cell seeding and handling methods had to be developed. According to this, proper positive and negative control samples had to be identified. The cultivation procedures were carried out using osteoblast-like murine fibroblasts (MC3T3-E1) and primary human osteoblasts (hOB). We could provide evidence that cultivation of these cells in our BioMEMS is feasible. In this context the relevant materials and the system's structure can be regarded as to be biocompatible. We could show that cell seeding and handling methods possess a strong impact on growth, development, and cellular activity of cell cultures in BioMEMS. Statistical biocompatibility data for the materials used is given. Biotechnol. Bioeng. 2011;108: 687-693. (C) 2010 Wiley Periodicals, Inc.