This study evaluated the use of a controlled exposure chamber and calibration cell to investigate the performance of open-path remote sensing instruments for workplace monitoring of pollutants. An open-path infrared spectrometer was deployed in a chamber, and a range of homogeneous air concentrations were generated using the tracer gas sulfur hexafluoride (SF6). Open-path measurements were compared with point-sample measurements taken along the beam and analyzed using an infrared (IR) and electron capture detector (ECD). A five-compartment calibration cell placed in the optical path was used to simulate heterogeneous concentrations of pollutants. Fifteen concentration patterns were created by injecting different volumes of SF6 into each compartment. Open-path spectrometer measurements were compared with compartment concentrations measured using an ECD. Results indicated that stable homogeneous and heterogeneous concentrations of SF6 were generated in the controlled exposure chamber and five-compartment calibration cell, respectively. Overall, individual open-path measurements were within 20% of point samples measured with the IR and ECDs. The open-path spectrometer measurements had a consistent positive bias of about 12%. Exposure chamber experiments uncovered remote sensing instrument design aspects that could adversely impact its use for indoor monitoring. The weight and size of the instrument make it useable only in a fixed position, thus limiting spatial coverage of the beam in a room. The instrument components were not airtight, resulting in overestimation of some open-path concentrations. A controlled test chamber and a long calibration cell placed in the optical path are useful tools for evaluating a variety of open-path spectrometer instrument performance issues relevant to industrial hygiene monitoring.