The influence of the use of estrogen replacement therapy (ERT) on the antidepressant response to sertraline of 127 women over 60 years old was evaluated with data from two multicenter trials. At endpoint, sertraline-treated women taking ERT had significantly greater global improvement and quality of life than those not receiving ERT. Modest improvements were also observed in anxiety symptoms and cognitive functioning. The results provide preliminary evidence that ERT use (without progesterone) in older depressed women may augment the antidepressant response to sertraline in terms of quality of life and general improvement.