Plasma or serum concentrations of imipramine [an antidepressant] and 5 of its nonconjugated metabolites (desipramine, 2-OH-imipramine, 2-OH-desipramine, imipramine-N-oxide and didesipramine) were followed in 3 cases of imipramine overdose and during steady state in 24 patients on continuous imipramine treatment. In the overdose cases the imipramine and desipramine concentrations declined monoexponentially with t1/2 [half-life] of 12-21 and 31-37 h. The 2-OH-imipramine and 2-OH-desipramine levels were lower and declined in parallel with their corresponding parent compounds. In the patients on continuous imipramine treatment, the steady-state levels of 2-OH-imipramine and 2-OH-desipramine were very low or immeasurable (< 15 nmol/l) in 5 patients. In most patients (n = 18) the hydroxymetabolite levels were much higher with 2-OH-imipramine/imipramine ratios of 0.09-0.45 and 2-OH-desipramine/desipramine ratios of 0.36-0.86. In 1 patient there were particularly high ratios (2-OH-imipramine/imipramine, 0.85; 2-OH-desipramine/desipramine, 1.30). The patients with very low hydroxymetabolite levels had considerably higher desipramine levels than the others, indicating that the low metabolite levels were due to poor hydroxylation. In 1 of these poor hydroxylators a desipramine t1/2 of .apprx. 120 h was estimated after imipramine discontinuation. With increased imipramine dose the 2-OH-imipramine levels tended to rise little or not at all. Imipramine-N-oxide could only be detected in the overdose cases during the 1st 6-12 h and didesipramine was generally present only when the desipramine levels were > 200 nmol/l.