Detailed mathematical models of chromatographic separation processes is of crucial importance due to the increased application of this separation technique in the downstream processes of the biotechnological, pharmaceutical and fine chemical industries. In this paper, a detailed dynamic model of a high performance liquid chromatographic unit was experimentally verified and used as the basis for the optimisation of a preparative chromatographic separation using closed-loop recycling operation. Results confirmed that tile effective column length could be increased by as much as 200% by recycling the feed sample back to the column for further purification with a concomitant improvement in purity and yield of the process. Data is presented to show the limitations of the method and the influence of key variables on column performance. Q 2001 Elsevier Science Ltd. All rights reserved.