A procedure is described which permits the determination of maprotiline in biological fluids for concentrations in the range of 10 to 1000 ng/ml. It relies on the use of N-desmethylclomipramine as internal standard, on derivatization of the secondary amines with heptafluorobutyric anhydride, and the use of gas chromatography with electron-capture detection. The method is linear, specific, accurate and precise. It is suitable for routine analyses and is particularly applicable for monitoring the levels of maprotiline in the blood of patients treated for depressive illness.