Following amitriptyline or imipramine overdose by 30 patients, total plasma concentrations ranged from 29 to 1732 ng/ml but did not correlate well with physical findings or most electrocardiographic changes. Only those patients with a QRS interval greater than 0.1 second had significantly elevated plasma levels. However, a plasma level ratio of the parent drug (amitriptyline, imipramine) to its respective N-desmethyl metabolite (nortriptyline, desmethylimipramine) greater than or equal to 2.0 was associated with an acute overdose. This ratio was more useful than total plasma levels in differentiating an overdose from a therapeutic dose with associated toxicity and an elevated steady-state plasma level.