1. The safety and efficacy of sertraline in the treatment of moderate-to-severe major depression in elderly outpatients, aged 60 years and older, with comorbid vascular disease was evaluated. 2. An analysis of the pooled results for the sertraline treatment group drawn from two prospective, randomized, double-blind studies (sertraline vs. fluoxetine, and sertraline vs. nortriptyline) was done. Patients were retrospectively categorized into one of 3 clinical groups: 1) patients with a current diagnosis of hypertension but no other past or present cardiovascular illness (HTN), 2) patients reporting a current or past history of cardiovascular illness, but excluding hypertension (VASC), and 3) patients with no hypertension, and no other comorbid vascular illness (NoVASC). Patients received 12-3. weeks of double-blind treatment with sertraline in flexible daily doses in the range of 50 - 150 mg (in the nortriptyline comparator trial) or 50 - 100 mg (in the fluoxetine comparator trial). 4. Sertraline treatment yielded comparable levels of response in all 3 groups (response criterion: CGI-much or very much improved) at treatment endpoint on both a completer analysis (HTN, 86%; VASC, 89%; NoVASC, 77%) and significantly higher response rates on a 12-week endpoint analysis (HTN, 74%; VASC, 69%; NoVASC, 58%; p < 0.05). Sertraline treatment was well-tolerated, with no between-group differences in rates of adverse events, or in discontinuation due to adverse events. Patients taking 5 or more concomitant medications showed no difference, when compared with patients taking none-or-one concomitant medication, either in rates of adverse events, or in discontinuation due to adverse events. 5. Sertraline was found to be a safe, well-tolerated, and effective as an antidepressant in elderly patients suffering from hypertension and other forms of vascular comorbidity.