The determination of mevalonic acid by gas chromatography/mass spectrometry (GC/MS) is complicated by poor extractability and multiple product formation. Reliable quantification down to physiological levels was achieved by isolating mevalonic acid by liquid partition chromatography and quantifying the underivatized lactone by means of ammonia chemical ionization, selected ion monitoring, capillary GC/MS. (2H3)mevalonic acid served as the internal standard. The method appears to be suitable for the study of mevalonic aciduria as well as the evaluation of different therapeutic regimens in patients with hypercholesterolaemia.