Simulated moving bed (SMB) chromatography has become a key separation technology in the areas of pharmaceutical and biotechnology industry thanks to its high productivity and short process development times. Today, modeling, design, and optimization of the SMB process are regarded to be well established. On the other hand, long term robust/optimized operation of the process is still an open issue. The common practice is to operate the SMB units under suboptimal operating conditions in order to gain the necessary robustness. The operating parameters are tuned manually by experienced operators in order to maintain the product specifications in the long term. Therefore, as SMB applications spread, the SMB process control problem becomes increasingly important. Recently, we have proposed an on-line optimization based SMB control scheme that allows exploiting the full economic potential of the SMB technology on the basis of minimal information. This work addresses the experimental implementation of the developed control concept on an eight-column four-section laboratory SMB unit that is used to separate the binary mixture of nucleosides uridine and guanosine. The performance of the SMB control scheme is demonstrated via several experimental controlled SMB runs that are designed to challenge the robust performance of the controller. The reported results aim to demonstrate that the controller is able to deliver the products with the specified purities and to optimize the process performance despite uncertainties in the system behavior and disturbances taking place during the operation. (c) 2006 American Institute of Chemical Engineers.