Single oral dose kinetics of nortriptyline and of its 2 major metabolites, conjugated and unconjugated 10-hydroxynortriptyline, were studied in 8 healthy subjects and 15 patients with chronic renal failure, 5 of whom were being treated with hemodialysis. Nortriptyline kinetics were unaltered, but the elimination of the metabolites was reduced in both groups of patients. In chronic renal failure the excretion of nortriptyline metabolites appeared to be the rate-limiting step in nortriptyline elimination. Depressed hemodialysis patients [3] were treated with nortriptyline (75 mg at night) for 6 wk. The ratios of the steady-state plasma concentrations of unconjugated 10-hydroxynortriptyline (0.74-2.30) were in the same range as those in a control group of depressed patients with adequate renal function (0.53-4.08) who were receiving nortriptyline. Conjugated 10-hydroxynortriptyline in renal failure patients was slow to reach steady-state concentrations and these were 10-20 times as high as those of the control depressed patients. Conjugated 10-hydroxynortriptyline in dialysis fluid during treatment showed that a mean 43 .+-. 7% of the dose was removed by a 10-h dialysis. Dialysis clearance of conjugated 10-hydroxynortriptyline was 58 .+-. 8 ml/min, but nortriptyline and unconjugated 10-hydroxynortriptyline were not appreciably removed by dialysis. Hemodialysis is not likely to be of value in the management of acute nortriptyline poisoning.