A method for the simultaneous measurement of dothiepin and two of its major metabolites, northiaden and dothiepin S-oxide in both plasma and whole blood is described. The method involves the use of gas chromatography-mass fragmentography. It is selective, sensitive (1 microgram/1) and reproducible. It has been used to analyse both plasma and blood samples following single oral doses of 75 mg dothiepin in seven volunteers.