The authors assessed the impact of osteopathic manipulative treatment (OMT) as an adjunct to standard psychiatric treatment of women with depression. Premenopausal women with newly diagnosed depression were randomly assigned to either control (osteopathic structural examination only; n = 9) or treatment group (OMT; n = 8). Both groups received conventional therapy consisting of the antidepressant paroxetine (Paxil) hydrochloride plus weekly psychotherapy for 8 weeks. Attending psychiatrists and psychologists were blinded to group assignments. No significant differences existed between groups for age or severity of disease. After 8 weeks, 100% of the OMT treatment group and 33% of the control group tested normal by psychometric evaluation. No significant differences or trends were observed between groups in levels of cytokine production (IL-1, IL-10, IL-2, IL-4, and IL-6) or in levels of anti-HSV-1, anti-HSV-2, and anti-EBV antibody. There was no pattern to the osteopathic manipulative structural dysfunctions recorded. The findings of this pilot study indicate that OMT may be a useful adjunctive treatment for alleviating depression in women.