We present a method for measuring seven commonly used tricyclic antidepressants in plasma. This method is suitable for monitoring therapeutic concentrations and for screening drug overdoses in cases where the identity of the abused tricyclic antidepressant may not be known. Drugs from alkalinized plasma are extracted into hexane in one step; two injections into the gas chromatograph/mass spectrometer follow. The tertiary amines (amitriptyline, doxepin, and imipramine) are analyzed by direct injection; the secondary amines (nortriptyline, desmethyldoxepin, desipramine, and protriptyline) are analyzed after derivitization with trifluoroacetic anhydride. Clomipramine and desmethyltrimipramine are suitable internal standards. Chemical ionization mass fragmentography, with methane as the reactant gas, is used. While maintaining specificity for these drugs, concentrations in human plasma ranging from 5 to 500 microng/liter can be measured. The coefficients of variation are about 4 to 11%.