Objectives-To simplify the current preparation of samples, and to improve the specificity and reliability of the conventional analytical methods to measure urinary alkoxyacetic acids. Methods-Samples containing alkoxyacetic acids including methoxy, ethoxy, and butoxyacetic acids (MAA, EAA, and BAA) were acidified with HCl and extracted with a mixed solvent of methylene chloride and isopropyl alcohol, then analysed by gas chromatography/mass spectrometry (GC/MS). Results-Optimal results were obtained when pH was 1.05-1.45, the ratio of methylene chloride and isopropyl alcohol was 2:1, and when extraction time was 10 minutes. Over the concentration range 0.3-200 µg/ml, MAA, EAA, and BAA could be determined with a pooled coeYcient of variation (nine concentrations, six replicate samples) of 5.55%, 6.37%, and 6.41%, respectively. Urine samples were stable for at least 5 months and 3 freeze-thaw cycles at −20°C. The limits of detection of MAA, EAA, and BAA were 0.055, 0.183, and 0.009 µg/ml, respectively. The matrix eVect of urine samples was negligible for MAA and EAA, but were marginally significant for BAA. The average recoveries of alkoxyacetic acids were 99%-101%. In urine samples MAA from 15 exposed workers showed a strong linear correlation (r=0.999, slope=1.01) between the new GC/MS method and Sakai's GC method. Conclusions-The simplified non-derivatisation pretreatment of samples coupled with GC/MS can provide a specific, sensitive, simple, safe, and reliable method for the biological monitoring of occupational exposure of ethylene glycol ethers. (Occup Environ Med 1999;56:460-467)