A system which combines intravenous microdialysis sampling on-line with fast microbore liquid chromatographic analysis is described. Using a 14 mm x 1 mm I.D. ODS column, caffeine, theobromine and paraxanthine could be resolved in under 1 min and acetaminophen and its two main metabolites, the glucuronide and sulfate conjugates, could be resolved in 30 s. This fast separation allowed on-line microdialysis sampling to be conducted with a 1-min sampling interval. The system was evaluated by monitoring the pharmacokinetics following intravenous administration of acetaminophen and caffeine.