A reversed-phase isocratic HPLC method is described for the determination of baclofen in human plasma. Solid-phase extraction using a SCX Bond Elut column is used followed by derivatization with o-phthalaldehyde-tert.-butanethiol and electrochemical detection. Both the within- and between-day R.S.D. and inaccuracy are less than 10% and 7%, respectively, even at the limit of quantification of the method, i.e., 10 ng/ml. The method was shown to give optimum performance in terms of sensitivity, precision and accuracy for the pharmacokinetic study of baclofen after a single oral administration to volunteers.