Among patients with major depressive disorder (MDD), physical and somatic symptoms are associated with a high degree of disability and healthcare utilization. However, little is known regarding the treatment of these symptoms with standard pharmacotherapy. To measure somatic symptoms of depression, the authors administered The Symptom Questionnaire (Kellner) before and after 8 weeks of open-label treatment with fluoxetine, 20 mg/day, in 170 MDD outpatients (mean age: 40.4 years). Somatic symptom scores decreased significantly after fluoxetine treatment. The degree of reduction in somatic symptoms was significantly and positively correlated with the degree of improvement in depressive symptoms as measured by the 17-item Hamilton Rating Scale for Depression (Ham-D). Somatic symptom scores at baseline did not predict the degree of reduction in Ham-D scores during treatment. However, fluoxetine-remitters had significantly lower somatic symptom scores at end-point than responders who did not remit. Taken together, these findings suggest that developing treatment strategies that successfully target somatic symptoms of depression may further improve the ability to treat depression to remission.