Diclofenac sodium (Voltaren;sodium[O-(2,6-dichloroanilino)phenyl]acetate), an effective, well-tolerated anti-inflammatory agent, is almost completely metabolized in humans and animals. The present article describes an automated procedure involving liquid-liquid extraction and subsequent HPLC analysis to determine unchanged diclofenac in human plasma. This procedure offers several advantages over current manual GC and HPLC methods. The transfer of the original manual procedure to an automated robotic system, with custom-made modules for solvent evaporation and HPLC injection, is described, and a comparison between the manual and automated procedure is drawn. The robotic method gave satisfactory accuracy and precision in the range of 0.02 to 3 micrograms/mL, with a quantitation limit of 0.02 micrograms/mL.