The Agency for Health Care Policy and Research Depression Guideline Panel recommended pharmacotherapy as the 1st-line treatment for more severely depressed primary care patients, but research supporting its recommendation has not been conducted with this population. A post hoc analysis was conducted, therefore, with data gathered in a randomized controlled trial about the relationship between initial level of depressive severity and functional ability, treatment with nortriptyline hydrochloride (NT) or interpersonal psychotherapy (IPT), and clinical course over 8 months among primary care patients experiencing major depression. Treatment type was unrelated to clinical course among more severely depressed patients (baseline 17-item Hamilton Rating Scale for Depression [HRSD] score > or = 20). However, less severely depressed patients (baseline 17-item HRSD score < or = 19) who were prescribed NT improved significantly more rapidly during the initial 3 months of treatment than patients provided with IPT.