A sensitive, specific, and quantitative GLC method is described for the determination of phendimetrazine in plasma, serum, or urine. An internal standard was used, which was extracted along with the drug. This mixture then was acetylated to improve the chromatographic separation. A concentration as low as 2 ng/ml of phendimetrazine could be measured from 2 ml of sample using a nitrogen-phosphorous detector. Linearity extended from 2 to 500 ng/ml, and the coefficient of variation was 7%. The method was shown to be applicable to a single-dose bioavailability study.