A sensitive and specific combined gas chromatographic-mass fragmentographic method for the determination of trazodone in rat plasma is described. After extraction with diethyl ether and washing of the extracts in order to prevent interference from endogenous materials, trazodone and the internal standard benperidol were separated on an OV-1 column. The minimum amount of trazodone detected was 20 ng by gas chromatography with the use of a flame ionization detector and 200 pg when using the mass fragmentographic technique. Plasma levels in rats treated with a single intravenous dose (10 mg/kg) of trazodone are also reported.