Liquid column chromatography with automatic sample presentation makes it possible to automate some laborious procedures of the clinical chemistry laboratory. It is feasible accurately and automatically to determine a single substance in numerous specimens. To demonstrate the potential of this technique, we successfully adapted to commercially available equipment the Maickel and Miller fluorescent o-phthalaldehyde reaction with indole derivatives, for determining 5-hydroxyindoleacetic acid (5-HIAA) in urine. Automated cation-exchange chromatography combined with the o-phthalaldehyde reaction affords excellent specificity and sensitivity. Analysis time, including regeneration of the resin, is about 30 min per sample, and when the sample plate is loaded, the instrument runs unattended. Parallel determinations with a manual solvent extraction procedure give good correlation. Although the instrumentation is costly, adaptation of such determinations as 5-HIAA will justify wider use of this versatile tool.