The pharmacokinetics of doxepin (DX) was studied in 21 Saudi patients treated long term with oral doses of this tricyclic antidepressant agent. The mean (SEM) values of the dose-normalized steady-state concentration and the apparent clearance after oral administration of this drug were 25.8 (4.8) ng.ml-1/mg.kg-1 and 2.529 (0.342) 1.h-1.kg-1, respectively. The pharmacokinetics of imipramine (IMI) was also studied in 30 Saudi patients who received oral doses of this drug for long durations. The mean dose-normalized steady-state concentration of IMI was 68.3 (19.7) ng.ml-1/mg.kg-1, and the mean apparent clearance after oral administration of IMI was 1.619 (0.353) 1.h-1. kg-1. The mean (SEM) ratio of the steady-state concentration of the metabolite desipramine (DES) to that of IMI (DES/IMI) was 0.873 (0.151). Using this value and the ratio of the mean apparent clearance after oral administration (TCL) of DES to that of IMI, the fraction of IMI metabolized to DES was calculated to be 0.489. The TCL of DES was estimated from data obtained for three additional patients who received oral doses of this drug for long durations. A mean value of 0.907 (0.351) 1.h-1.kg-1 was obtained.