The aim of this study was to develop an exposure system which enables in vitro experiments to be conducted under variously modulated radiofrequency exposures. Based on the evaluation of different possible systems, it was decided to realize a system based on rectangular waveguides. The system was optimized for the following parameters: (1) homogeneity of the cell exposure, (2) simultaneous exposure of several Petri dishes, (3) efficiency, (4) strict environmental control, (5) quick and easy access to the Petri dishes, (6) cost, and (7) simple operation by non-engineering personnel. The implemented control software enables investigation of a wide spectrum of amplitude modulation schemes between 0.1 Hz and 1 kHz, including the modulation schemes of current and future digital mobile communication systems as well as other exposure protocols. The system described has been initially utilized for a study on the differentiation and cell functions of embryonic stem cells. Detailed numerical and experimental dosimetry and environmental tests have demonstrated that it meets all target objectives. The entire system including the sham exposure system fits into a single incubator. It enables the carrying out of various experiments designed to test biological responses to RF exposures at 1.2–1.7 GHz by using various modulation schemes and long term exposure protocols as well as simultaneous data logging.